Herbicides

ABSTRACT

The present invention relates to herbicidally active pyridino-/pyrimidino-pyridine derivatives. The invention further provides processes and intermediates used for the preparation of such derivatives. The invention further extends to herbicidal compositions comprising such derivatives, as well as to the use of such compounds and compositions in controlling undesirable plant growth: in particular the use in controlling weeds, in crops of useful plants.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/087,074, filed Sep. 20, 2018, which is a 371 National Stageapplication of International Application No. PCT/EP2017/056291, filedMar. 16, 2017, which claims priority to GB 1604970.2, filed Mar. 23,2016, the entire contents of these applications are hereby incorporatedby reference.

The present invention relates to herbicidally activepyridino-/pyrimidino-pyridine derivatives, as well as to processes andintermediates used for the preparation of such derivatives. Theinvention further extends to herbicidal compositions comprising suchderivatives, as well as to the use of such compounds and compositions incontrolling undesirable plant growth: in particular the use incontrolling weeds, in crops of useful plants.

Certain pyrido-pyridine and pyrimidino-pyridine derivatives are knownfrom JP2014-208631, where they are stated to have activity asinsecticidal agents, and in particular miticidal agents.

The present invention is based on the finding that pyridino-pyridine,and pyrimidino-pyridine, derivatives of Formula (I) as defined herein,exhibit surprisingly good herbicidal activity. Thus, according to thepresent invention there is provided a compound of Formula (I)

or a salt or N-oxide thereof, wherein,

X¹ is N or CR¹;

R¹ is selected from the group consisting of hydrogen, halogen, cyano,C₁-C₆alkyl, C₃-C₆cycloalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆alkoxy,—C(O)OC₁-C₆alkyl, —S(O)_(p)C₁-C₆alkyl, NR⁶R⁷, C₁-C₆haloalkoxy andC₁-C₆haloalkyl;

R² is selected from the group consisting of halogen, cyano, nitro,C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,—C(O)OC₁-C₆alkyl, —S(O)_(p)(C₁-C₆alkyl), C₁-C₆alkoxy andC₁-C₆haloalkoxy;

R³ is —C(O)R⁹;

R⁴ is selected from the group consisting of hydrogen, C₁-C₆alkyl,C₁-C₆haloalkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C_(r)alkoxyC_(s)alkyl,—C_(r)alkoxyC_(s)haloalkyl, C_(r)alkoxyC_(s)thioalkyl, —C(O)R⁹ and—(CR^(a)R^(b))_(q)R⁵;

each R^(a) is independently hydrogen or C₁-C₂ alkyl;

each R^(b) is independently hydrogen or C₁-C₂ alkyl;

R^(c) is hydrogen or C₁-C₄alkyl;

R⁵ is —C(O)OC₁-C₆alkyl, —C₃-C₆cycloalkyl, cyano, —NR⁶R⁷,—C(O)NR^(a)R^(b), —S(O)_(p)(R¹¹)_(n), -aryl or -heteroaryl wherein saidaryl and heteroaryl are optionally substituted by 1 to 3 independent R⁸;

R⁶ and R⁷ are independently selected from the group consisting ofhydrogen and C₁-C₆alkyl;

each R⁸ is independently selected from the group consisting of halogen,C₁-C₆ alkyl and C₁-C₆alkoxy-, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy-, cyanoand S(O)_(p)(C₁-C₆alkyl);

each R⁹ is independently selected from the group consisting of hydrogen,C₁-C₆alkyl, C_(r)alkoxyC_(s)alkyl, C₁-C₆haloalkyl,C_(r)alkoxyC_(s)haloalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, and—(CR^(a)R^(b))_(q)R¹⁰;

or R⁴ and R⁹ together with the atoms to which they are joined form a 5-7membered ring system containing from 1 to 3 heteroatoms, wherein atleast one heteroatom is N, and any additional heteroatom isindependently selected from S, O and N;

R¹⁰ is —C(O)OR^(c), —OC(O)R^(c), —C₃-C₆cycloalkyl, or an -aryl,-aryloxy, -heteroaryl, -heteroaryloxy or -heterocyclyl ring, whereinsaid ring is optionally substituted by 1 to 3 independent R⁸;

each n is independently 0 or 1;

p is 0, 1, or 2;

each q is independently 0, 1, 2, 3, 4, 5 or 6;

r is 1, 2, 3, 4, or 5, s is 1, 2, 3, 4, or 5, and the sum of r+s is lessthan or equal to 6; and

R¹¹ is C₁-C₆alkyl.

Compounds of formula (I) may exist as different geometric isomers, or indifferent tautomeric forms. This invention covers the use of all suchisomers and tautomers, and mixtures thereof in all proportions, as wellas isotopic forms such as deuterated compounds.

It may be the case that compounds of formula (I) may contain one or moreasymmetric centers and may thus give rise to optical isomers anddiastereomers. While shown without respect to stereochemistry, thepresent invention includes the use of all such optical isomers anddiastereomers as well as the racemic and resolved, enantiomerically pureR and S stereoisomers and other mixtures of the R and S stereoisomersand agrochemically acceptable salts thereof.

Each alkyl moiety either alone or as part of a larger group (such asalkoxy, alkylthio, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl,ordialkylaminocarbonyl, et al.) may be straight-chained or branched.Typically, the alkyl is, for example, methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl,neopentyl, or n-hexyl. The alkyl groups are generally C₁-C₆ alkyl groups(except where already defined more narrowly), but are preferably C₁-C₄alkyl or C₁-C₃ alkyl groups, and, more preferably, are C₁-C₂ alkylgroups (such as methyl).

Alkenyl and alkynyl moieties can be in the form of straight or branchedchains, and the alkenyl moieties, where appropriate, can be of eitherthe (E)- or (Z)-configuration. Alkenyl and alkynyl moieties can containone or more double and/or triple bonds in any combination; butpreferably contain only one double bond (for alkenyl) or only one triplebond (for alkynyl).

The alkenyl or alkynyl moieties are typically C₂-C₄ alkenyl or C₂-C₄alkynyl, more specifically ethenyl (vinyl), prop-2-enyl, prop-3-enyl(allyl), ethynyl, prop-3-ynyl (propargyl), or prop-1-ynyl. Preferably,the term cycloalkyl refers to cyclopropyl, cyclobutyl, cyclopentyl orcyclohexyl.

In the context of the present specification the term “aryl” preferablymeans phenyl.

Heteroaryl groups and heteroaryl rings (either alone or as part of alarger group, such as heteroaryl-alkyl-) are ring systems containing atleast one heteroatom and can be in mono- or bi-cyclic form. Preferably,single rings will contain 1, 2 or 3 ring heteroatoms selectedindependently from nitrogen, oxygen and sulfur. Typically “heteroaryl”is as used in the context of this invention includes furyl, thienyl,pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazolyl,thiazolyl, isothiazolyl, oxadiazolyl, pyridyl, pyrimidinyl, pyridazinyl,pyrazinyl, and triazinyl rings, which may or may not be substituted asdescribed herein.

The term “heterocyclyl” as used herein, encompasses ring systemscontaining at least one heteroatom and that are typically in monocyclicform. Preferably, heterocyclyl groups will contain up to two heteroatomswhich will preferably be chosen from nitrogen, oxygen and sulfur. Wherea heterocycle contains sulfur as a heteroatom it may be in oxidized formi.e. in the form —S(O)_(p)— where p is an integer of 0, 1 or 2 asdefined herein. Such heterocyclyl groups are preferably 3- to8-membered, and more preferably 3- to 6-membered rings. Examples ofheterocyclic groups include oxetanyl, thietanyl, and azetidinyl groups.Such heterocyclylic rings may or may not be substituted as describedherein.

Halogen (or halo) encompasses fluorine, chlorine, bromine or iodine. Thesame correspondingly applies to halogen in the context of otherdefinitions, such as haloalkyl or halophenyl.

Haloalkyl groups having a chain length of from 1 to 6 carbon atoms are,for example, fluoromethyl, difluoromethyl, trifluoromethyl,chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl,2-fluoroethyl, 2-chloroethyl, pentafluoroethyl,1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and2,2,2-trichloroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl.

Alkoxy groups preferably have a chain length of from 1 to 6 carbonatoms. Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy,n-butoxy, isobutoxy, sec-butoxy or tert-butoxy or a pentyloxy orhexyloxy isomer, preferably methoxy and ethoxy. It should also beappreciated that two alkoxy substituents may be present on the samecarbon atom.

Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy,trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy,2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy or2,2,2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy ortrifluoromethoxy.

C₁-C₆ alkyl-S— (alkylthio) is, for example, methylthio, ethylthio,propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio ortert-butylthio, preferably methylthio or ethylthio.

C₁-C₆ alkyl-S(O)— (alkylsulfinyl) is, for example, methylsulfinyl,ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl,isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferablymethylsulfinyl or ethylsulfinyl.

C₁-C₆ alkyl-S(O)₂— (alkylsulfonyl) is, for example, methylsulfonyl,ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl,isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferablymethylsulfonyl or ethylsulfonyl.

Compounds of formula (I) may form, and/or be used as, agronomicallyacceptable salts with amines (for example ammonia, dimethylamine andtriethylamine), alkali metal and alkaline earth metal bases orquaternary ammonium bases. Among the alkali metal and alkaline earthmetal hydroxides, oxides, alkoxides and hydrogen carbonates andcarbonates used in salt formation, emphasis is to be given to thehydroxides, alkoxides, oxides and carbonates of lithium, sodium,potassium, magnesium and calcium, but especially those of sodium,magnesium and calcium. The corresponding trimethylsulfonium salt mayalso be used.

Compounds of formula (I) may also form (and/or be used as) agronomicallyacceptable salts with various organic and/or inorganic acids, forexample, acetic, propionic, lactic, citric, tartaric, succinic, fumaric,maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic,phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic,benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly knownacceptable acids, when the compound of formula (I) contains a basicmoiety.

Where appropriate compounds of formula (I) may also be in the formof/used as an N-oxide.

Compounds of formula (I) may also be in the form of/used as hydrateswhich may be formed during the salt formation.

Preferred values of X¹, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹,R^(a), R^(b), R^(c), n, p, q, r, and s are as set out below, and acompound of formula (I) according to the invention may comprise anycombination of said values. The skilled person will appreciate thatvalues for any specified set of embodiments may combined with values forany other set of embodiments where such combinations are not mutuallyexclusive.

The skilled man will appreciate that the values or r and s in thedefinitions C_(r)alkoxyC_(s)alkyl, C_(r)alkoxyC_(s)thioalkyl, andC_(r)alkoxyC_(s)haloalkyl are such that the length of the carbon chainwithin the substituent does not exceed 6. Preferred values of r are 1,2, or 3. Preferred values for s are 1, 2, or 3. In various embodiments ris 1, s is 1; or, r is 1, s is 2; or r is 1, s is 3; or r is 2, s is 1;r is 2, s is 2; or r is 2, s is 3; or r is 3, s is 1; or r is 3, s is 2,r is 3, s is 3. Particularly preferred substituents thus includemethoxymethyl, methoxybutyl, and ethoxymethyl, as well asmethylthiomethyl and ethyl thiomethyl.

In one particular embodiment of the present invention, X¹ is N.

In another embodiment of the present invention, X¹ is CR¹. R¹ ispreferably halogen or cyano, more preferably fluoro, chloro or cyano.

Most preferably X¹ is N or CF.

Preferably R² is halogen, cyano, C₁-C₆alkyl or C₁-C₆haloalkyl. Morepreferably R² is cyano, methyl or trifluoromethyl, Even more preferablyR² is methyl or trifluoromethyl. Most preferably R² is trifluoromethyl.

Examples of preferred R³ groups for use in the invention may be derivedfrom the preferences for R⁹ and the definitions therein. Particularlypreferred R³ groups are as defined within Table 1 below. Preferably R⁴is selected from the group consisting of hydrogen, C₁-C₄alkyl,C₃-C₆alkenyl, C_(r)alkoxyC_(s)alkyl, C_(r)alkylthioC_(s)alkyl,C₃-C₆alkynyl, C₁-C₃haloalkyl, C_(r)alkoxyC_(s)haloalkyl, —C(O)R⁹, and(CR^(a)R^(b))_(q)R⁵. In such embodiments where R⁴ is —C(O)R⁹, it ispreferred that R⁹ is C₁-C₃alkyl, C₂-C₄alkenyl, or —(CR^(a)R^(b))_(q)R¹⁰.More preferably when R⁴ is —C(O)R⁹, R⁹ is hydrogen, -methyl, ethyl,propyl, butenyl, or —(CH₂)₂C(O)OR^(c).

Where R⁴ is (CR^(a)R^(b))_(q)R⁵, in one set of embodiments, q is 1, 2,or 3; R^(a) and R^(b) are independently hydrogen, methyl or ethyl(preferably hydrogen), and R⁵ is —C(O)NR^(a)R^(b), —NR⁶R⁷, cyano, or—C₃-C₆cycloalkyl (e.g. cyclopropyl), -aryl (e.g. phenyl) or -heteroaryl(in particular a 5- or 6-membered heteroaryl, such as for example,thiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, or triazinylring), wherein said aryl and heteroaryl are optionally substituted by 1to 3 independent R⁸.

In such embodiments where R⁵ is —C(O)NR^(a)R^(b), R^(a) and R^(b) arepreferably independently hydrogen, methyl or ethyl (more preferablymethyl).

Where R⁵ is an optionally substituted heteroaryl ring, it isparticularly preferred that said ring is a pyridyl or thiazolyl ring.

In an alternative embodiment of the present invention, R⁴ and R⁹together with the atoms to which they are joined form a 5-7 memberedring system containing from 1 to 3 heteroatoms, wherein at least oneheteroatom is N, and any additional heteroatom is independently selectedfrom S, O and N. Preferably said ring system is a 5- or 6-memberedN-linked heterocyclic ring system, and more preferably it is apyrrolidinone, pyrrolidinedione or piperidinone ring. The skilled manwill appreciate that the R⁹ in these embodiments derives from R³.

Preferably each R^(a) is independently hydrogen, methyl or ethyl, morepreferably hydrogen or methyl.

Preferably each R^(b) is independently hydrogen, methyl or ethyl, morepreferably hydrogen or methyl.

Preferably each q is independently 0, 1, 2 or 3. The skilled man willappreciate that if q is 0 when R⁴ is (CR^(a)R^(b))_(q)R⁵, then R⁴ isequivalent to R⁵. Similarly if q is 0 when R⁹ is (CR^(a)R^(b))_(q)R¹⁰,then R⁹ is equivalent to R¹⁰.

Preferably each R^(c) is hydrogen, methyl or ethyl.

In one particular embodiment R⁶ and R⁷ are both hydrogen. In anotherembodiment R⁶ is hydrogen and R⁷ is C₁-C₆alkyl (e.g., methyl or ethyl).In another embodiment, R⁶ and R⁷ are both C₁-C₆alkyl, in particular bothmethyl or both ethyl.

Where an aryl, aryloxy, heteroaryl, heteroaryloxy, or heterocyclic ringsystem is substituted by 1 to 3 independent R⁸ as described herein, itis preferred that such ring system is substituted by 1 or 2 independentR⁸, more preferably by 1 R⁸. Preferably each R⁸ is independentlyselected from halogen or C₁-C₃ alkyl, C₁-C₃haloalkyl. More preferablyeach R⁸ is independently fluoro, chloro or methyl.

Preferably R⁹ is C₁-C₆alkyl [preferably methyl, ethyl, propyl (inparticular/so-propyl) or butyl (in particular tert-butyl)],C₁-C₃haloalkyl, C₁-C₃alkoxyC₁-C₃alkyl or (CR^(a)R^(b))_(q)R¹⁰.

R¹⁰ is preferably —C(O)OR^(c), —OC(O)R^(c), cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, or a ring system selected from phenyl, phenoxy,pyridinyl, pyrimidinyl, thiazolyl, and thiophenyl, wherein said ringsystem is optionally substituted by 1-3 independent R⁸.

Table 1 below provides 115 specific examples of herbicidal compounds ofFormula (I) for use according to the invention.

TABLE 1 Specific examples of compounds of Formula (I) Entry No X¹ R² R³R⁴ C1 C—F CH₃ C(O)CH(CH₃)₂ C(O)CH(CH₃)₂ C2 N CH₃ C(O)CH(CH₃)₂ H C3 C—FCH₃ C(O)CH(CH₃)₂ H C4 C—F CF₃ C(O)CH(CH₃)₂ CH₃ C5 C—F CF₃ C(O)CH₃C(O)CH₃ C6 N CF₃ C(O)CH₃ C(O)CH₃ C7 N CF₃ C(O)CH₃ H C8 N CF₃C(O)CH(CH₃)₂ H C9 C—F CF₃ C(O)CH₃ H C10 C—F CF₃ C(O)CH(CH₃)₂ H C11 C—CNCF₃ C(O)CH(CH₃)₂ H C12 C−Cl CF₃ C(O)CH(CH₃)₂ H C13 C—F CF₃ C(O)CH₂CH₃ HC14 C—F CF₃ C(O)Ph H C15 C—F CF₃ C(O)CH₂CH₃ CH₃ C16 C—F CF₃ C(O)CH(CH₃)₂CH₂CH═CH₂ C17 N CF₃ C(O)Ph H C18 N CF₃ C(O)CH₂CH₃ H C19 C—F CF₃ C(O)CH₂cyclohexyl H C20 C—F CF₃ C(O) cyclohexyl H C21 C—F CF₃ C(O) cyclobutyl HC22 C—F CF₃ C(O)CH₂CH₂CH₃ H C23 C—F CF₃ C(O)CH═CHCH₃ (E) H C24 C—F CF₃C(O)CH₂CH₂OCH₃ H C25 C—F CF₃ C(O)CH₂ cyclopentyl H C26 C—F CF₃ C(O)CHCl₂H C27 C—F CF₃ C(O)CH₂OCH₃ H C28 C—F CF₃ C(O)CH₂O phenyl H C29 C—F CF₃C(O)CCl₃ H C30 C—F CF₃ C(O)p-toluene H C31 C—F CF₃ C(O)-2,6-di-F—Ph HC33 C—F CF₃ C(O)-2,4,5-tri-F—Ph H C34 C—F CF₃ C(O)t-Bu H C35 C—F CF₃C(O)CH₂Cl H C36 C—F CF₃ C(O)C(CH₃)₂OC(O)CH₃ H C37 C—F CF₃ C(O)CH═C(CH₃)₂H C38 C—F CF₃ C(O)CH═C(CH₃)₂ C(O)CH═C(CH₃)₂ C39 C—F CF₃ C(O)CH₂CH₃CH₂CH═CH₂ C42 C—F CF₃ C(O)CH₂CO₂CH₂CH₃ H C44 C—F CF₃ C(O)CH₂CH₃C(O)CH₂CH₃ C45 C—F CF₃ C(O)-pyridin-2-yl H C46 C—F CF₃ C(O)-2-F—Ph H C47C—F CF₃ C(O)-thiophen-2-yl H C49 C—F CF₃ C(O)CH₂CH₂CH₂CH₃ H C50 C—F CF₃C(O)-pyridin-3-yl H C51 C—F CF₃ C(O)-3-CH₃- H thiophen-2-yl C52 C—F CF₃C(O)-5-CH₃- H thiophen-2-yl C53 C—F CF₃ C(O)CH₂CH₂ H cyclopentyl C54 C—FCF₃

C55 C—F CF₃

C56 C—F CF₃ C(O)CH₂CF₃ H C57 C—F CF₃ C(O)CH₂CH₃ CH₂CN C58 C—F CF₃C(O)CH(CH₃)₂ CH₂CN C59 C—F CF₃ C(O) cyclopropyl H C60 N CF₃ C(O)CCl₃ HC61 C—F CF₃ C(O)CH(CH₃)₂ CH₂CCH C62 C—F CF₃ C(O)CH₂CH₃ CH₂CH₂CHF₂ C63C—F CF₃ C(O)CH₂OCH₃ CH₂CH═CH₂ C65 N CF₃ C(O)CHCl₂ H C66 C—F CF₃ C(O)CH₂cyclopropyl H C67 C—F CF₃

C68 C—F CF₃ C(O)CCl₃ CH₃ C69 C—F CF₃ C(O)CH(CH₃)₂ (CH₂)₃N(CH₂CH₃)₂ C70C—F CF₃ C(O)CH₂CH₃

C71 C—F CF₃ C(O)CH₂CH₃ CH₂C(O)N(CH₃)₂ C72 C—F CF₃ C(O)CH₂CH₃ CH₂OCH₂CF₃C73 C—F CF₃ C(O)CH₂CH₃ CH₂CH═C(CH₃)₂ C74 C—F CF₃ C(O)Ph (CH₂)₃N(CH₂CH₃)₂C75 C—F CF₃ C(O)Ph CH₂CH(CH₃)₂ C76 C—F CF₃ C(O)Ph CH₂OCH₂C(CH₃)₃ C77 C—FCF₃ C(O)Ph

C78 C—F CF₃ C(O)Ph

C79 C—F CF₃ C(O)CH₂OCH₃ CH₂CH(CH₃)₂ C80 C—F CF₃ C(O)CH₂OCH₃ CH₂cyclopropyl C81 C—F CF₃ C(O)CH₂OCH₃ CH₂OCH₂C(CH₃)₃ C82 C—F CF₃C(O)CH₂OCH₃

C83 C—F CF₃ C(O)CH₂OCH₃

C84 C—F CF₃ C(O)CH₂OCH₃ CH₂C(O)N(CH₃)₂ C85 C—F CF₃ C(O)CH(CH₃)₂CH₂CH₂OCH₃ C86 C—F CF₃ C(O)CH(CH₃)₂ CH₂CH(CH₃)₂ C87 C—F CF₃ C(O)CH(CH₃)₂CH₂ cyclopropyl C88 C—F CF₃ C(O)CH(CH₃)₂ CH₂CH₂SCH₃ C89 C—F CF₃C(O)CH(CH₃)₂ CH₂OCH₂C(CH₃)₃ C90 C—F CF₃ C(O)CH(CH₃)₂ CH(CH₃)₂ C91 C—FCF₃ C(O)CH(CH₃)₂

C92 C—F CF₃ C(O)CH(CH₃)₂

C93 C—F CF₃ C(O)CH(CH₃)₂ CH₂CH═C(CH₃)₂ C94 C—F CF₃ C(O)CH₂CH₃ CH₂CCH C95C—F CF₃ C(O)CH₂CH₃ (CH₂)₃N(CH₂CH₃)₂ C96 C—F CF₃ C(O)CH₂CH₃ CH₂CH₂OCH₃C97 C—F CF₃ C(O)CH₂CH₃ CH₂CH(CH₃)₂ C98 C—F CF₃ C(O)CH₂CH₃ CH₂CH₂SCH₃ C99C—F CF₃ C(O)CH₂CH₃ CH₂OCH₂C(CH₃)₃ C100 C—F CF₃ C(O)CH₂CH₃ CH(CH₃)₂ C101C—F CF₃ C(O)CH₂CH₃

C102 C—F CF₃ C(O)CH₂CH₃

C103 C—F CF₃ C(O)Ph CH₂ cyclopropyl C104 C—F CF₃ C(O)Ph CH₂CH₂SCH₃ C105C—F CF₃ C(O)Ph CH₂C(O)N(CH₃)₂ C106 C—F CF₃ C(O)CH₂OCH₃ CH₂CH═C(CH₃)₂C107 C—F CF₃ C(O)CH(CH₃)₂ CH₂C(O)N(CH₃)₂ C108 C—F CF₃ C(O)CH₂CH₃ CH₂cyclopropyl C109 N CF₃ C(O) cyclopropyl H C110 N CF₃

C111 C—F CF₃ C(O)cyclopentyl H C112 C—F CF₃ C(O)H H C113 C—F CF₃C(O)CH₂CH₂CO₂H H C114 C—F CN C(O)CH₂OCH₃ H C115 C—F CN C(O)CH₂CH₃ H C116N CN C(O)CH₂CH₃ H C117 C—F CF₃

H C118 C—F CF₃ C(O)CH₂CH₂CO₂CH₃ H C119 C—F CF₃ C(O)CH₂CH₂CO₂CH₃C(O)CH₂CH₂CO₂CH₃ C120 C—F CF₃

H C121 C—F CF₃ C(O)CH₂CH₃ C(O)CH₂CH₃

Compounds of Formula (I) may be prepared according to the followingschemes, in which the substituents X¹, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸,R⁹, R¹⁰, R¹¹, R^(a), R^(b), R^(c), n, p, q, r, and s have (unlessotherwise stated explicitly) the definitions described hereinbefore,using techniques known to the person skilled in the art of organicchemistry. General methods for the production of compounds of formula(I) are described below. The starting materials used for the preparationof the compounds of the invention may be purchased from the usualcommercial suppliers or may be prepared by known methods. The startingmaterials as well as the intermediates may be purified before use in thenext step by state of the art methodologies such as chromatography,crystallization, distillation and filtration.

Typical abbreviations used throughout are as follows:

-   Ac=acetyl-   app=apparent-   BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl-   br.=broad-   Bu=tert-butyl-   t-BuOH=tert-butanol-   d=doublet-   dd=double doublet-   Dba=dibenzyiideneacetone-   DCM=dichloromethane-   DMF=N, A/-dimethylformamide-   DMSO=dimetbylsuifoxide-   DPPA=diphenyipbosphoryl azide-   Et₃N=triethyiamine-   Et₂O=diethyl ether-   EtOAc=ethyl acetate-   EtOH=ethanol-   m=muttipiet-   mCPBA=mefa-chloro-perbenzoic acid-   Me=methyl-   MeOH=methanol-   Ms=mesylate-   Ph=phenyl-   q=quartet-   RT=room temperature-   s=singlet-   t=triplet-   Tf=trifiate-   TEA=trifluoroacetic acid-   THF=tetrahydrofuran-   IMS=tetramethyisiiane-   tr=retention time

Processes for preparation of compounds of the present invention, whichoptionally can be in the form of an agrochemically acceptable salt, arenow described, and form further aspects of the present invention.

Compounds of Formula Ia are compounds of Formula I where R³ is COR⁹,compounds of Formula Ib are compounds of Formula I where both R³ and R⁴are COR⁹.

A compound of Formula Ic, which is a compound of Formula I where n=1,may be prepared from a compound of Formula I where n=0 via reaction witha suitable oxidant in a suitable solvent. Suitable oxidants may include3-chloroperbenzoic acid (see for example UCB Pharma WO2012032334).Suitable solvents may include DCM.

A compound of Formula Ia may be prepared from a compound of Formula Avia an amide formation reaction with a compound of Formula B in thepresence of a suitable base (where LG¹ is a suitable activated leavinggroup such as F, Cl or pentafluorophenol) optionally (when LG¹ is OH orOR) in the presence of a suitable amide coupling reagent and in asuitable solvent. Suitable bases include pyridine or triethylamine.Suitable amide coupling reagents include 1-propanephosphonic acid cyclicanhydride (see for example Vertex Pharmaceuticals Inc, WO2010/048564).Suitable solvents include DCM, DCE, THF or Me-THF. Compounds of formulaB are commercially available or may be prepared by methods well known inthe literature.

In an alternative approach, a compound of Formula Ia may be preparedfrom a compound of Formula Iaa (a compound of formula I where R⁴ ishydrogen) via an alkylation reaction with a compound of Formula D in thepresence of a suitable base and in a suitable solvent. Suitable basesinclude sodium hydride (see for example Bioorg. Med. Chem. Lett. (2010)4911). Suitable solvents include THF or DMF. Compounds of Formula D arecommercially available or may be prepared by methods well known in theliterature.

A compound of Formula Ib may be prepared from a compound of Formula Iaavia an amide formation reaction with a compound of Formula B, in thepresence of a suitable base (when LG¹ is a suitable activated leavinggroup such as F, Cl or pentafluorophenol) and in a suitable solvent.Suitable bases may include pyridine or triethylamine. Suitable solventsmay include DCM or DCE. Compounds of formula B are commerciallyavailable or may be prepared by methods well known in the literature.

In an alternative approach, a compound of Formula I may be prepared froma compound of Formula E (where Y² is a suitable halogen, such as Cl, Bror I or a suitable pseudohalogen, such as OTf) via a cross-couplingreaction with a compound of Formula F, optionally in the presence of asuitable catalyst/ligand system, optionally in the presence of asuitable base and in a suitable solvent. Suitable catalyst/ligandsystems include CuI/N,N-dimethyl-1,2-diaminocyclohexane (see for exampleC. Enguehard-Gueiffer et al Synthesis (2015) 3983) orCuI/N-methyl-(methylamino)ethylamine (see for example TemperaPharmaceuticals Inc WO2013/019682). Suitable bases include potassiumphosphate and suitable solvents may include toluene or 1,4-dioxane.Compounds of Formula F are commercially available or may be prepared bymethods well known in the literature.

A compound of Formula E may be prepared from a compound of Formula G(where Y¹ is a suitable halogen, such as Cl or Br) via a cross-couplingreaction with a compound of Formula H (where Q is a suitable couplinggroup, such as —B(OH)₂ or —B(OR)₂ or —SnR₃) in the presence of asuitable catalyst, optionally in the presence of a suitable base and ina suitable solvent. Suitable catalysts may include Pd(PPh₃)₄ (see forexample Vertex Pharmaceuticals Ltd. WO2011087776), Pd₂Cl₂(PPh₃)₂ (seefor example Abbott Laboratories US2012245124) or[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (see forexample Dow Agro Sciences US2013005574). Suitable bases may includeK₂CO₃ or CsF. Suitable solvents may include ethylene glycol dimethylether, acetonitrile, DMF, ethanol, 1,4-dioxane and/or water. Compoundsof Formula G and of Formula H are commercially available or can beprepared by methods well known in the literature.

In a yet further alternative approach, a compound of Formula I may beprepared from a compound of Formula J (where Y¹ is a suitable halogen,such as Cl, Br or I or a suitable pseudohalogen, such as OTf) via across-coupling reaction with a compound of Formula H (where Q is asuitable coupling group, such as —B(OH)₂ or —B(OR)₂ or —SnR₃) in thepresence of a suitable catalyst, optionally in the presence of asuitable base and in a suitable solvent. Suitable catalysts may includePd(PPh₃)₄ (see for example Vertex Pharmaceuticals Ltd. WO2011087776 orS. M. Bromidge et al J. Med. Chem. (2000) 1123), Pd₂Cl₂(PPh₃)₂ (see forexample Abbott Laboratories US2012245124),[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (see forexample Dow Agro Sciences US2013005574). Suitable bases may includeK₂CO₃ or CsF. Suitable solvents may include ethylene glycol dimethylether, acetonitrile, DMF, ethanol, 1,4-dioxane and/or water. Compoundsof Formula H are commercially available or can be prepared by methodswell known in the literature.

A compound of Formula J may be prepared from a compound of Formula L(where Y¹ is a suitable halogen, such as Br or I or a suitablepseudohalogen, such as OTf via reaction with a compound of Formula K,optionally in the presence of a suitable catalyst/ligand system andoptionally in the presence of a suitable base and in a suitable solvent.Suitable catalyst/ligand systems includeCuI/N,N-dimethyl-1,2-diaminocyclohexane (see for example C.Enguehard-Gueiffer et al Synthesis (2015) 3983) orCuI/N-methyl-(methylamino)ethylamine (see for example TemperoPharmaceuticals Inc WO2013/019682). Suitable bases include potassiumphosphate and suitable solvents may include toluene or 1,4-dioxane.Compounds of Formula K and of Formula L are commercially available ormay be prepared by methods well known in the literature.

A compound of Formula Aa (a compound of Formula A where R⁴ is hydrogen)may be prepared from a compound of Formula M via a reduction reactionoptionally in the presence of a suitable catalyst and/or using asuitable reducing agent in a suitable solvent. Suitable catalystsinclude palladium on charcoal (see for example Z. Gao et al Bioorg. Med.Chem. Lett. (2013) 6269), Raney nickel (see for example MilleniumPharmaceuticals Ltd WO2010/065134). Suitable reducing agents includehydrogen gas, Fe/HCl (see for example A. Gangee et al J. Med. Chem.(1998) 4533), SnCl₂ (see for example Pharmacia and Upjohn CompanyWO2004/099201). Suitable solvents include ethanol, methanol, ethylacetate or water.

In an alternative approach, a compound of Formula Aa may be preparedfrom a compound of Formula N via a Curtius rearrangement using asuitable reagent in a suitable solvent. Suitable reagents include DPPA(see for example Takeda Pharmaceutical Company Ltd WO2008/156757) andsuitable solvents include DMF or toluene.

A compound of Formula M may be prepared from a compound of Formula O(where Y¹ is a suitable halogen, such as Cl, Br or I or suitablepseudohalogen, such as OTf) via a cross-coupling reaction with acompound of Formula H (where Q is a suitable coupling group, such as—B(OH)₂ or —B(OR)₂ or —SnR₃) in the presence of a suitable catalyst,optionally in the presence of a suitable base and in a suitable solvent.Suitable catalysts may include Pd(PPh₃)₄ (see for example A. P. Johnsonet al, ACS Med. Chem. Lett. (2011) 729) or[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (see forexample Laboratories Almirall, WO2009/021696). Suitable bases mayinclude K₂CO₃, Na₂CO₃, Cs₂CO₃, K₃PO₄ or CsF. Suitable solvents mayinclude ethylene glycol dimethyl ether, acetonitrile, DMF, ethanol,1,4-dioxane, tetrahydrofuran and/or water. Compounds of Formula H and ofFormula O are commercially available or can be prepared by methods wellknown in the literature.

A compound of Formula N may be prepared from a compound of Formula P(where R^(x) is C₁₋₆ alkyl) via a hydrolysis reaction in the presence ofa suitable reagent in a suitable solvent. Suitable reagents include NaOH(see for example F. Giordanetto et al Bioorg. Med. Chem. Lett (2014),2963), LiOH (see for example AstraZeneca AB, WO2006/073361) or KOH (seefor example Kowa Co. Ltd EP1627875). Suitable solvents include H₂O, THF,MeOH or EtOH or mixtures thereof.

In an alternative approach, a compound of Formula N may be prepared froma compound of Formula Q (where Y¹ is a suitable halogen, such as Cl orBr) via a cross-coupling reaction with a compound of Formula H (where Qis a suitable coupling group, such as —B(OH)₂ or —B(OR)₂ or —SnR₃) inthe presence of a suitable catalyst, optionally in the presence of asuitable base and in a suitable solvent. Suitable catalysts may includePd(PPh₃)₄ (see for example Pfizer Limited WO2009/153720) or[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (see forexample AstraZeneca AB, WO2009/075160). Suitable bases may includeK₂CO₃, Na₂CO₃, Cs₂CO₃, K₃PO₄ or CsF. Suitable solvents may includeethylene glycol dimethyl ether, acetonitrile, DMF, ethanol, 1,4-dioxane,tetrahydrofuran and/or water. Compounds of Formula H are commerciallyavailable or can be prepared by methods well known in the literature.

A compound of Formula R may be prepared from a compound of Formula S(where Y¹ is a suitable halogen, such as Cl or Br) via a cross-couplingreaction with a compound of Formula H (where Q is a suitable couplinggroup, such as —B(OH)₂ or —B(OR)₂ or —SnR₃) in the presence of asuitable catalyst, optionally in the presence of a suitable base and ina suitable solvent. Suitable catalysts may include Pd(PPh₃)₄ (see forexample Pfizer Limited WO2009/153720) or[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (see forexample Cytokinetics Incorporated WO2008/016643). Suitable bases mayinclude K₂CO₃, Na₂CO₃, Cs₂CO₃, K₃PO₄ or CsF. Suitable solvents mayinclude ethylene glycol dimethyl ether, acetonitrile, DMF, ethanol,1,4-dioxane, tetrahydrofuran and/or water. Compounds of Formula H arecommercially available or can be prepared by methods well known in theliterature.

A compound of Formula S (where Y¹ is a suitable halogen, such as Br orC₁) may be prepared from a compound of Formula T via a halogenationreaction using a suitable reagent, optionally in a suitable solvent.Suitable reagents may include POCl₃ (see for example TakedaPharmaceutical Co. Ltd. US2011/152273). Suitable solvents may includeDCM or DCE.

A compound of Formula T may be prepared from a compound of Formula U viaan oxidation reaction using a suitable oxidising reagent in a suitablesolvent. Suitable oxidants may include 3-chloroperbenzoic acid (see forexample Thus Therapeutics Inc. US2012/023875) or urea hydrogen peroxidecomplex/trifluoroacetic anhydride (see Takeda Pharmaceutical Co. Ltd.US2011/152273). Suitable solvents include DCM or acetonitrile. Compoundsof Formula U are commercially available or can be prepared by methodswell known in the literature.

In a yet further alternative approach, compounds of Formula R may beprepared from compounds of Formula Y by reaction with compounds ofFormula Z in the presence of ammonium acetate (see for example F.Hoffmann-La Roche WO2008/034579). Compounds of Formula Z arecommercially available or can be prepared by methods well known in theliterature.

Compounds of Formula Y may be prepared from compounds of Formula AA byreaction with dimethyl formamide dimethylacetal (see for example F.Hoffmann-La Roche WO2008/034579). Compounds of Formula AA arecommercially available or can be prepared by methods well known in theliterature.

In a yet further alternative approach, a compound of Formula R may beprepared from a compound of Formula AB via a reduction using a suitablereducing agent optionally in a suitable solvent. Suitable reducingagents include indium/ammonium chloride (see for example J. S. Yadav etal Tet. Lett (2000), 2663) or zinc/ammonium chloride. Suitable solventsmay include MeOH, THF or water or combinations thereof.

A compound of Formula AB made be prepared from a compound of Formula Tvia a cross-coupling reaction with a compound of Formula AC (where Y² isa suitable halogen, such as Cl, Br or I or suitable pseudohalogen, suchas OTf) in the presence of a suitable catalyst, optionally in thepresence of a suitable base and in a suitable solvent. Suitablecatalysts include Pd(OAc)₂/tri(tert-butyl)phosphoniumtetrafluoroboronate (see for example F. Glorius et al JACS (2013)12204). A suitable base is K₂CO₃. A suitable solvent is toluene.Compounds of Formula AC are commercially available or can be prepared bymethods well known in the literature.

The compounds of Formula (I) as described herein may be used asherbicides by themselves, but they are generally formulated intoherbicidal compositions using formulation adjuvants, such as carriers,solvents and surface-active agents (SFAs). Thus, the present inventionfurther provides a herbicidal composition comprising a herbicidalcompound as described herein and an agriculturally acceptableformulation adjuvant. The composition can be in the form of concentrateswhich are diluted prior to use, although ready-to-use compositions canalso be made. The final dilution is usually made with water, but can bemade instead of, or in addition to, water, with, for example, liquidfertilisers, micronutrients, biological organisms, oil or solvents.

Such herbicidal compositions generally comprise from 0.1 to 99% byweight, especially from 0.1 to 95% by weight of compounds of Formula (I)and from 1 to 99.9% by weight of a formulation adjuvant, whichpreferably includes from 0 to 25% by weight of a surface-activesubstance.

The compositions can be chosen from a number of formulation types, manyof which are known from the Manual on Development and Use of FAOSpecifications for Plant Protection Products, 5th Edition, 1999. Theseinclude dustable powders (DP), soluble powders (SP), water solublegranules (SG), water dispersible granules (WG), wettable powders (WP),granules (GR) (slow or fast release), soluble concentrates (SL), oilmiscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (EO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, capsule suspensions (CS) and seed treatmentformulations. The formulation type chosen in any instance will dependupon the particular purpose envisaged and the physical, chemical andbiological properties of the compound of Formula (I).

Dustable powders (DP) may be prepared by mixing a compound of Formula(I) with one or more solid diluents (for example natural clays, kaolin,pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk,diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulphur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of Formula (I)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulphate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of Formula(I) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of Formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound ofFormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of Formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulphates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof Formula (I) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallisation in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of Formula (I) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment.

Preparation of an EW involves obtaining a compound of Formula (I) eitheras a liquid (if it is not a liquid at room temperature, it may be meltedat a reasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsifying theresultant liquid or solution into water containing one or more SFAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SFAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound ofFormula (I) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in in ECs or in EWs. An ME may be either anoil-in-water or a water-in-oil system (which system is present may bedetermined by conductivity measurements) and may be suitable for mixingwater-soluble and oil-soluble pesticides in the same formulation. An MEis suitable for dilution into water, either remaining as a microemulsionor forming a conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound ofFormula (I). SCs may be prepared by ball or bead milling the solidcompound of Formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of Formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of Formula (I) and a suitablepropellant (for example n-butane). A compound of Formula (I) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurised, hand-actuated spray pumps.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerisationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of Formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound ofFormula (I) and they may be used for seed treatment. A compound ofFormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

The composition may include one or more additives to improve thebiological performance of the composition, for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of Formula (I).Such additives include surface active agents (SFAs), spray additivesbased on oils, for example certain mineral oils or natural plant oils(such as soy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of Formula (I)).

Wetting agents, dispersing agents and emulsifying agents may be SFAs ofthe cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SFAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulphuric acid (for example sodium laurylsulphate), salts of sulphonated aromatic compounds (for example sodiumdodecylbenzenesulphonate, calcium dodecylbenzenesulphonate,butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ethersulphates (for example sodium laureth-3-sulphate), ether carboxylates(for example sodium laureth-3-carboxylate), phosphate esters (productsfrom the reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulphosuccinamates, paraffin or olefine sulphonates, taurates andlignosulphonates.

Suitable SFAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SFAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetylalcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

Herbicidal compositions as described herein may further comprise atleast one additional pesticide. For example, the compounds of formula(I) can also be used in combination with other herbicides or plantgrowth regulators. In a preferred embodiment the additional pesticide isa herbicide and/or herbicide safener. Examples of such mixtures are, inwhich T represents a compound of Formula (I), I+acetochlor,I+acifluorfen, I+acifluorfen-sodium, I+aclonifen, I+acrolein,I+alachlor, I+alloxydim, I+ametryn, I+amicarbazone, I+amidosulfuron,I+aminopyralid, I+amitrole, I+anilofos, I+asulam, I+atrazine,I+azafenidin, I+azimsulfuron, I+BCPC, I+beflubutamid, I+benazolin,I+bencarbazone, I+benfluralin, I+benfuresate, I+bensulfuron,I+bensulfuron-methyl, I+bensulide, I+bentazone, I+benzfendizone,I+benzobicyclon, I+benzofenap, I+bicyclopyrone, I+bifenox, I+bilanafos,I+bispyribac, I+bispyribac-sodium, I+borax, I+bromacil, I+bromobutide,I+bromoxynil, I+butachlor, I+butamifos, I+butralin, I+butroxydim,I+butylate, I+cacodylic acid, I+calcium chlorate, I+cafenstrole,I+carbetamide, I+carfentrazone, I+carfentrazone-ethyl, I+chlorflurenol,I+chlorflurenol-methyl, I+chloridazon, I+chlorimuron,I+chlorimuron-ethyl, I+chloroacetic acid, I+chlorotoluron,I+chlorpropham, I+chlorsulfuron, I+chlorthal, I+chlorthal-dimethyl,I+cinidon-ethyl, I+cinmethylin, I+cinosulfuron, I+cisanilide,I+clethodim, I+clodinafop, I+clodinafop-propargyl, I+clomazone,I+clomeprop, I+clopyralid, I+cloransulam, I+cloransulam-methyl,I+cyanazine, I+cycloate, I+cyclosulfamuron, I+cycloxydim, I+cyhalofop,I+cyhalofop-butyl, I+2,4-D, I+daimuron, I+dalapon, I+dazomet, I+2,4-DB,I+I+desmedipham, I+dicamba, I+dichlobenil, I+dichlorprop,I+dichlorprop-P, I+diclofop, I+diclofop-methyl, I+diclosulam,I+difenzoquat, I+difenzoquat metilsulfate, I+diflufenican,I+diflufenzopyr, I+dimefuron, I+dimepiperate, I+dimethachlor,I+dimethametryn, I+dimethenamid, I+dimethenamid-P, I+dimethipin,I+dimethylarsinic acid, I+dinitramine, I+dinoterb, I+diphenamid,I+dipropetryn, I+diquat, I+diquat dibromide, I+dithiopyr, I+diuron,I+endothal, I+EPTC, I+esprocarb, I+ethalfluralin, I+ethametsulfuron,I+ethametsulfuron-methyl, I+ethephon, I+ethofumesate, I+ethoxyfen,I+ethoxysulfuron, I+etobenzanid, I+fenoxaprop-P, I+fenoxaprop-P-ethyl,I+fentrazamide, I+ferrous sulfate, I+flamprop-M, I+flazasulfuron,I+florasulam, I+fluazifop, I+fluazifop-butyl, I+fluazifop-P,I+fluazifop-P-butyl, I+fluazolate, I+flucarbazone,I+flucarbazone-sodium, I+flucetosulfuron, I+fluchloralin, I+flufenacet,I+flufenpyr, I+flufenpyr-ethyl, I+flumetralin, I+flumetsulam,I+flumiclorac, I+flumiclorac-pentyl, I+flumioxazin, I+flumipropin,I+fluometuron, I+fluoroglycofen, I+fluoroglycofen-ethyl, I+fluoxaprop,I+flupoxam, I+flupropacil, I+flupropanate, I+flupyrsulfuron,I+flupyrsulfuron-methyl-sodium, I+flurenol, I+fluridone,I+flurochloridone, I+fluroxypyr, I+flurtamone, I+fluthiacet,I+fluthiacet-methyl, I+fomesafen, I+foramsulfuron, I+fosamine,I+glufosinate, I+glufosinate-ammonium, I+glyphosate, I+halauxifen,I+halosulfuron, I+halosulfuron-methyl, I+haloxyfop, I+haloxyfop-P,I+hexazinone, I+imazamethabenz, I+imazamethabenz-methyl, I+imazamox,I+imazapic, I+imazapyr, I+imazaquin, I+imazethapyr, I+imazosulfuron,I+indanofan, I+indaziflam, I+iodomethane, I+iodosulfuron,I+iodosulfuron-methyl-sodium, I+ioxynil, I+isoproturon, I+isouron,I+isoxaben, I+isoxachlortole, I+isoxaflutole, I+isoxapyrifop,I+karbutilate, I+lactofen, I+lenacil, I+linuron, I+mecoprop,I+mecoprop-P, I+mefenacet, I+mefluidide, I+mesosulfuron,I+mesosulfuron-methyl, I+mesotrione, I+metam, I+metamifop, I+metamitron,I+metazachlor, I+methabenzthiazuron, I+methazole, I+methylarsonic acid,I+methyldymron, I+methyl isothiocyanate, I+metolachlor, I+S-metolachlor,I+metosulam, I+metoxuron, I+metribuzin, I+metsulfuron,I+metsulfuron-methyl, I+molinate, I+monolinuron, I+naproanilide,I+napropamide, I+naptalam, I+neburon, I+nicosulfuron, I+n-methylglyphosate, I+nonanoic acid, I+norflurazon, I+oleic acid (fatty acids),I+orbencarb, I+orthosulfamuron, I+oryzalin, I+oxadiargyl, I+oxadiazon,I+oxasulfuron, I+oxaziclomefone, I+oxyfluorfen, I+paraquat, I+paraquatdichloride, I+pebulate, I+pendimethalin, I+penoxsulam,I+pentachlorophenol, I+pentanochlor, I+pentoxazone, I+pethoxamid,I+phenmedipham, I+picloram, I+picolinafen, I+pinoxaden, I+piperophos,I+pretilachlor, I+primisulfuron, I+primisulfuron-methyl, I+prodiamine,I+profoxydim, I+prohexadione-calcium, I+prometon, I+prometryn,I+propachlor, I+propanil, I+propaquizafop, I+propazine, I+propham,I+propisochlor, I+propoxycarbazone, I+propoxycarbazone-sodium,I+propyzamide, I+prosulfocarb, I+prosulfuron, I+pyraclonil,I+pyraflufen, I+pyraflufen-ethyl, I+pyrasulfotole, I+pyrazolynate,I+pyrazosulfuron, I+pyrazosulfuron-ethyl, I+pyrazoxyfen, I+pyribenzoxim,I+pyributicarb, I+pyridafol, I+pyridate, I+pyriftalid, I+pyriminobac,I+pyriminobac-methyl, I+pyrimisulfan, I+pyrithiobac,I+pyrithiobac-sodium, I+pyroxasulfone, I+pyroxsulam, I+quinclorac,I+quinmerac, I+quinoclamine, I+quizalofop, I+quizalofop-P,I+rimsulfuron, I+saflufenacil, I+sethoxydim, I+siduron, I+simazine,I+simetryn, I+sodium chlorate, I+sulcotrione, I+sulfentrazone,I+sulfometuron, I+sulfometuron-methyl, I+sulfosate, I+sulfosulfuron,I+sulfuric acid, I+tebuthiuron, I+tefuryltrione, I+tembotrione,I+tepraloxydim, I+terbacil, I+terbumeton, I+terbuthylazine, I+terbutryn,I+thenylchlor, I+thiazopyr, I+thifensulfuron, I+thiencarbazone,I+thifensulfuron-methyl, I+thiobencarb, I+topramezone, I+tralkoxydim,I+tri-allate, I+triasulfuron, I+triaziflam, I+tribenuron,I+tribenuron-methyl, I+triclopyr, I+trietazine, I+trifloxysulfuron,I+trifloxysulfuron-sodium, I+trifluralin, I+triflusulfuron,I+triflusulfuron-methyl, I+trihydroxytriazine, I+trinexapac-ethyl,I+tritosulfuron,I+[3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]aceticacid ethyl ester (CAS RN 353292-31-6). The compounds of formula (I)and/or compositions of the present invention may also be combined withherbicidal compounds disclosed in WO06/024820 and/or WO07/096576.

The mixing partners of the compound of Formula (I) may also be in theform of esters or salts, as mentioned e.g. in The Pesticide Manual,Sixteenth Edition, British Crop Protection Council, 2012.

The compound of Formula (I) can also be used in mixtures with otheragrochemicals such as fungicides, nematicides or insecticides, examplesof which are given in The Pesticide Manual (supra).

The mixing ratio of the compound of Formula (I) to the mixing partner ispreferably from 1:100 to 1000:1.

The mixtures can advantageously be used in the above-mentionedformulations (in which case “active ingredient” relates to therespective mixture of compound of Formula I with the mixing partner).

The compounds of Formula (I) as described herein can also be used incombination with one or more safeners. Likewise, mixtures of a compoundof Formula (I) as described herein with one or more further herbicidescan also be used in combination with one or more safeners. The safenerscan be AD 67 (MON 4660), benoxacor, cloquintocet-mexyl, cyprosulfamide(CAS RN 221667-31-8), dichlormid, fenchlorazole-ethyl, fenclorim,fluxofenim, furilazole and the corresponding R isomer, isoxadifen-ethyl,mefenpyr-diethyl, oxabetrinil,N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide (CAS RN221668-34-4). Other possibilities include safener compounds disclosedin, for example, EP0365484 e.gN-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.Particularly preferred are mixtures of a compound of Formula I withcyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and/orN-(2-methoxybenzoyl)-4-[(methyl-aminocarbonyl)amino]benzenesulfonamide.

The safeners of the compound of Formula (I) may also be in the form ofesters or salts, as mentioned e.g. in The Pesticide Manual (supra). Thereference to cloquintocet-mexyl also applies to a lithium, sodium,potassium, calcium, magnesium, aluminium, iron, ammonium, quaternaryammonium, sulfonium or phosphonium salt thereof as disclosed in WO02/34048, and the reference to fenchlorazole-ethyl also applies tofenchlorazole, etc.

Preferably the mixing ratio of compound of Formula (I) to safener isfrom 100:1 to 1:10, especially from 20:1 to 1:1.

The mixtures can advantageously be used in the above-mentionedformulations (in which case “active ingredient” relates to therespective mixture of compound of Formula (I) with the safener).

As described above, compounds of formula (I) and/or compositionscomprising such compounds may be used in methods of controlling unwantedplant growth, and in particular in controlling unwanted plant growth incrops of useful plants. Thus, the present invention further provides amethod of selectively controlling weeds at a locus comprising cropplants and weeds, wherein the method comprises application to the locus,of a weed-controlling amount of a compound of formula (I), or acomposition as described herein. ‘Controlling’ means killing, reducingor retarding growth or preventing or reducing germination. Generally theplants to be controlled are unwanted plants (weeds). ‘Locus’ means thearea in which the plants are growing or will grow.

The rates of application of compounds of Formula (I) may vary withinwide limits and depend on the nature of the soil, the method ofapplication (pre- or post-emergence; seed dressing; application to theseed furrow; no tillage application etc.), the crop plant, the weed(s)to be controlled, the prevailing climatic conditions, and other factorsgoverned by the method of application, the time of application and thetarget crop. The compounds of Formula I according to the invention aregenerally applied at a rate of from 10 to 2000 g/ha, especially from 50to 1000 g/ha.

The application is generally made by spraying the composition, typicallyby tractor mounted sprayer for large areas, but other methods such asdusting (for powders), drip or drench can also be used.

Useful plants in which the composition according to the invention can beused include crops such as cereals, for example barley and wheat,cotton, oilseed rape, sunflower, maize, rice, soybeans, sugar beet,sugar cane and turf.

Crop plants can also include trees, such as fruit trees, palm trees,coconut trees or other nuts. Also included are vines such as grapes,fruit bushes, fruit plants and vegetables.

Crops are to be understood as also including those crops which have beenrendered tolerant to herbicides or classes of herbicides (e.g. ALS-,GS-, EPSPS-, PPO-, ACCase- and HPPD-inhibitors) by conventional methodsof breeding or by genetic engineering. An example of a crop that hasbeen rendered tolerant to imidazolinones, e.g. imazamox, by conventionalmethods of breeding is Clearfield® summer rape (canola). Examples ofcrops that have been rendered tolerant to herbicides by geneticengineering methods include e.g. glyphosate- and glufosinate-resistantmaize varieties commercially available under the trade namesRoundupReady® and LibertyLink®, as well as those where the crop planthas been engineered to over-express homogentisate solanesyltransferaseas taught in, for example, WO2010/029311.

Crops are also to be understood as being those which have been renderedresistant to harmful insects by genetic engineering methods, for exampleBt maize (resistant to European corn borer), Bt cotton (resistant tocotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).Examples of Bt maize are the Bt 176 maize hybrids of NK® (SyngentaSeeds). The Bt toxin is a protein that is formed naturally by Bacillusthuringiensis soil bacteria. Examples of toxins, or transgenic plantsable to synthesise such toxins, are described in EP-A-451 878, EP-A-374753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examplesof transgenic plants comprising one or more genes that code for aninsecticidal resistance and express one or more toxins are KnockOut®(maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton),NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seedmaterial thereof can be both resistant to herbicides and, at the sametime, resistant to insect feeding (“stacked” transgenic events). Forexample, seed can have the ability to express an insecticidal Cry3protein while at the same time being tolerant to glyphosate.

Crops are also to be understood to include those which are obtained byconventional methods of breeding or genetic engineering and containso-called output traits (e.g. improved storage stability, highernutritional value and improved flavour).

Other useful plants include turf grass for example in golf-courses,lawns, parks and roadsides, or grown commercially for sod, andornamental plants such as flowers or bushes.

The compositions can be used to control unwanted plants (collectively,‘weeds’). The weeds to be controlled include both monocotyledonous (e.g.grassy) species, for example: Agrostis, Alopecurus, Avena, Brachiaria,Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium,Monochoria, Rottboeliia, Sagittaria, Scirpus, Setaria and Sorghum; anddicotyledonous species, for example: Abutilon, Amaranthus, Ambrosia,Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Kochia, Nasturtium,Polygonum, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola andXanthium. Weeds can also include plants which may be considered cropplants but which are growing outside a crop area (‘escapes’), or whichgrow from seed left over from a previous planting of a different crop(‘volunteers’). Such volunteers or escapes may be tolerant to certainother herbicides.

Preferably the weeds to be controlled and/or growth-inhibited, includemonocotyledonous weeds, more preferably grassy monocotyledonous weeds,in particular those from the following genus: Agrostis, Alopecurus,Apera, Avena, Brachiaria, Bromus, Cenchrus, Cyperus (a genus of sedges),Digitaria, Echinochloa, Eleusine, Eriochloa, Fimbristylis (a genus ofsedges), Juncus (a genus of rushes), Leptochloa, Lolium, Monochoria,Ottochloa, Panicum, Pennisetum, Phalaris, Poa, Rottboellia, Sagittaria,Scirpus (a genus of sedges), Setaria and/or Sorghum, and/or volunteercorn (volunteer maize) weeds; in particular: Alopecurus myosuroides(ALOMY, English name “blackgrass”), Apera spica-venti, Avena fatua(AVEFA, English name “wild oats”), Avena ludoviciana, Avena stehlis,Avena sativa (English name “oats” (volunteer)), Brachiaria decumbens,Brachiaria plantaginea, Brachiaria platyphylla (BRAPP), Bromus tectorum,Digitaria hohzontalis, Digitaria insularis, Digitaria sanguinalis(DIGSA), Echinochloa crusgalli (English name “common barnyard grass”,ECHCG), Echinochloa oryzoides, Echinochloa colona or colonum, Eleusineindica, Eriochloa villosa (English name “woolly cupgrass”), Leptochloachinensis, Leptochloa panicoides, Lolium perenne (LOLPE, English name“perennial ryegrass”), Lolium multiflorum (LOLMU, English name “Italianryegrass”), Lolium persicum (English name “Persian darnel”), Loliumrigidum, Panicum dichotomiflorum (PANDI), Panicum miliaceum (Englishname “wild proso millet”), Phalaris minor, Phalaris paradoxa, Poa annua(POAAN, English name “annual bluegrass”), Scirpus maritimus, Scirpusjuncoides, Setaria viridis (SETVI, English name “green foxtail”),Setaria faberi (SETFA, English name “giant foxtail”), Setaria glauca,Setaria lutescens (English name “yellow foxtail”), Sorghum bicolor,and/or Sorghum halepense (English name “Johnson grass”), and/or Sorghumvulgare; and/or volunteer corn (volunteer maize) weeds.

In one embodiment, grassy monocotyledonous weeds to be controlledcomprise weeds from the genus: Agrostis, Alopecurus, Apera, Avena,Brachiaria, Bromus, Cenchrus, Digitaria, Echinochloa, Eleusine,Eriochloa, Leptochloa, Lolium, Ottochloa, Panicum, Pennisetum, Phalaris,Poa, Rottboellia, Setaria and/or Sorghum, and/or volunteer corn(volunteer maize) weeds; in particular: weeds from the genus Agrostis,Alopecurus, Apera, Avena, Brachiaria, Bromus, Cenchrus, Digitaria,Echinochloa, Eleusine, Eriochloa, Leptochloa, Lolium, Panicum, Phalaris,Poa, Rottboeliia, Setaria, and/or Sorghum, and/or volunteer corn(volunteer maize) weeds.

In a further embodiment, the grassy monocotyledonous weeds are“warm-season” (warm climate) grassy weeds; in which case they preferablycomprise (e.g. are): weeds from the genus Brachiaria, Cenchrus,Digitaria, Echinochloa, Eleusine, Eriochloa, Leptochloa, Ottochloa,Panicum, Pennisetum, Phalaris, Rottboellia, Setaria and/or Sorghum,and/or volunteer corn (volunteer maize) weeds. More preferably, thegrassy monocotyledonous weeds, e.g. to be controlled and/orgrowth-inhibited, are “warm-season” (warm climate) grassy weedscomprising (e.g. being): weeds from the genus Brachiaria, Cenchrus,Digitaria, Echinochloa, Eleusine, Eriochloa, Panicum, Setaria and/orSorghum, and/or volunteer corn (volunteer maize) weeds.

In another particular embodiment the grassy monocotyledonous weeds, are“cool-season” (cool climate) grassy weeds; in which case they typicallycomprise weeds from the genus Agrostis, Alopecurus, Apera, Avena,Bromus, Lolium and/or Poa.

Various aspects and embodiments of the present invention will now beillustrated in more detail by way of example. It will be appreciatedthat modification of detail may be made without departing from the scopeof the invention.

PREPARATION EXAMPLES

Those skilled in the art will appreciate that depending on the nature ofthe substituents X¹, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹,R^(a), R^(b), R^(c), n, p, q, r, and s, compounds of Formula I may existin different interconvertible rotameric forms as described in, forexample S. A. Richards and J. C. Hollerton, Essential Practical NMR forOrganic Chemistry, John Wiley and sons (2010). For clarity, only thespectroscopic data for the major rotameric form is quoted.

General Methods

[Pd(IPr*)(cin)Cl] refers to the catalyst below—see Chem. Eur. J. 2012,18, 4517

Xantphos palladacycle 4th generation refers to the catalyst below—seeOrg. Lett. 2014, 16, 4296 and WO13184198.

JackiePhos Pd G3 refers to the catalyst below—see J. Am. Chem. Soc.,2009, 131, 16720.

tBuBrettPhos Pd G3 refers to the catalyst below—see Org. Lett., 2013,15, 1394

Example P1: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-2-methyl-propanamide(Compound C10)

Step 1: Synthesis of ethyl1-oxido-2-(trifluoromethyl)pyridin-1-ium-3-carboxylate

To a stirred suspension of freshly ground urea hydrogen peroxideaddition compound (0.099 g, 1.05 mmol) in DCM (10 mL) at 0° C. was addedethyl 2-(trifluoromethyl)pyridine-3-carboxylate (0.1 g, 0.46 mmol)followed by slow addition (ca. 5 minutes) of a solution oftrifluoroacetic anhydride (0.13 mL, 0.91 mmol) in DCM (5 mL). Thereaction was allowed to warm to ambient and left stirring overnight. Thereaction was washed with 2M aq. sodium carbonate solution (5 mL) and 2Maq sodium metabisulphite solution (2×10 mL) and the solvent was removedin vacuo. The crude product was purified via flash column chromatographyon silica gel using an EtOAc/Hexane gradient as eluent to give thedesired product (76 mg, 73%) as a thick colourless oil.

¹H NMR (400 MHz, CDCl₃) δ 8.28 (1H, d), 7.44 (1H, dd), 7.21 (1H, d),4.43 (2H, q), 1.44 (3H, t)

Step 2: Synthesis of ethyl6-chloro-2-(trifluoromethyl)pyridine-3-carboxylate

A mixture of ethyl1-oxido-2-(trifluoromethyl)pyridin-1-ium-3-carboxylate (0.2 g, 0.85mmol) and POCl₃ (2 mL, 21.24 mmol) was heated to 80° C. for 6 hours andthen cooled to ambient. The reaction was quenched with 2M aq Na₂CO₃solution and then extracted with Et₂O (3×15 mL). The combined organicextracts were dried over Na₂SO₄ and pre-absorbed onto silica gel forpurification via flash column chromatography on silica using anEtOAc/isohexane gradient as eluent to give the desired product (0.14 g,61%) as a colourless oil.

¹H NMR (400 MHz, CDCl₃) δ 8.09 (d, 1H), 7.60 (d, 1H), 4.43 (q, 2H), 1.43(t, 3H).

Step 3: Synthesis of 6-chloro-2-(trifluoromethyl)pyridine-3-carboxylicacid

To a solution of ethyl6-chloro-2-(trifluoromethyl)pyridine-3-carboxylate (190 mg, 0.75 mmol)in THF (4 mL) and H₂O (2 mL) was added LiOH.H₂O (72 mg, 1.72 mmol) andthe reaction stirred at room temperature for 3 h. The reaction wasconcentrated under reduced pressure and 2N HCl was added slowly to reachpH 3-4, then extracted with EtOAc (2×10 mL). The combined organicextracts were dried over MgSO₄ and concentrated to dryness under reducedpressure to give the desired product (170 mg, quant) as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 8.12 (1H, d), 7.62 (1H, d)

Step 4: Synthesis of tert-butylN-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamate

To a stirred solution of6-chloro-2-(trifluoromethyl)pyridine-3-carboxylic acid (3.0 g, 13.3mmol) in f-butanol (25 mL) was added triethylamine (2.41 mL, 17.29 mmol)and diphenylphosphoryl azide (DPPA) (3.73 mL, 17.29 mmol). The reactionwas heated at 90° C. for 2 hrs and then was allowed to cool to roomtemperature overnight. The reaction mixture was diluted with ethylacetate and washed with water (×2), then brine (×1), dried over MgSO₄and evaporated to dryness under reduced pressure. The crude product wasadsorbed onto silica and purified by flash chromatography on silicausing a gradient from 5-50% ethyl acetate in isohexane as eluent to givethe desired product (3.24 g, 82%) as a colourless oil.

¹H NMR (400 MHz, CDCl₃) δ 8.64 (d, 1H), 7.48 (d, 1H), 6.89 (br.s, 1H),1.52 (s, 9H)

Step 5: Synthesis of tert-butylN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]carbamate

To a stirred suspension of (5-fluoro-3-pyridyl)boronic acid (1.70 g, 12mmol), Xantphos palladacycle 4th generation (0.2 g, 0.21 mmol) andtert-butyl N-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamate (2.50 g,8.4 mmol) in a mixture of ethanol (6.8 mL) and toluene (25 mL) was addedK₂CO₃ (8.4 mL of a 2M in water, 17 mmol). The reaction mixture washeated at reflux for 3 hrs. The reaction mixture was cooled to roomtemperature and concentrated to dryness. The residue was adsorbed ontosilica and purified by flash chromatography on silica using a gradientfrom 5-100% EtOAc/isohexane as eluent to give the desired compound (2.57g, 85%).

¹H NMR (400 MHz, CDCl₃) δ 9.02 (dd, 1H), 8.79 (d, 1H), 8.52 (d, 1H),8.12 (m, 1H), 7.94 (d, 1H), 7.01 (br.s, 1H), 1.56 (s, 9H)

Step 6: Synthesis of6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridin-3-amine

Trifluoroacetic acid (1.4 mL, 18 mmol) was added to tert-butylN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]carbamate (685mg, 1.92 mmol) in DCM (7 mL) and the reaction mixture was heated atreflux for 3 h before being allowed to cool to room temperature. Thereaction mixture was partitioned between 2M NaOH (so pH of aqueous wasgreater than 12) and DCM. The aqueous layer was extracted twice with DCMand the combined organic extracts were dried over MgSO₄ and dry loadedon to celite.

Purification by flash chromatography on silica using a gradient of 0-30%EtOAc in isohexane as eluent gave the desired compound (472 mg, 96%) asa white solid.

¹H NMR (400 MHz, CDCl₃) δ 8.93 (m, 1H), 8.45 (d, 1H), 8.12-8.00 (m, 1H),7.75 (d 1H), 7.21 (d, 1H), 4.38 (br.s, 2H)

Step 7: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-2-methyl-propanamide

To a stirred solution of6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridin-3-amine (423 mg, 1.64mmol) and pyridine (0.54 mL, 6.58 mmol) in DCM (20 mL) was addeddropwise 2,2-dimethylpropanoyl chloride (3.2894 mmol, 0.405 mL). Thereaction was stirred at room temperature overnight. The reaction wasthen concentrated on to silica and purified by flash chromatography onsilica using an EtOAc/isohexane gradient as eluent to give the desiredcompound (0.41 g, 76%) as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 9.07 (br.s, 1H), 8.78 (d, 1H), 8.52 (1H, br.s), 8.12 (m, 1H), 7.92 (d, 1H), 7.67 (br.s, 1H), 2.58 (m, 1H), 1.31 (d,6H)

Example P2: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]acetamide(Compound C9)

Step 1: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]acetamide

To a stirred solution of6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridin-3-amine (0.05 g, 0.194mmol) in DCM (5 mL) was added pyridine (0.064 mL, 0.78 mmol) and aceticanhydride (0.038 mL, 0.39 mmol,). The resultant pale yellow solution wasleft to stand at RT for 72 hours. The reaction was concentrated in vacuoand purified via flash chromatography on silica using an EtOAc/isohexanegradient as eluent to give the desired product (16 mg, 27%).

¹H NMR (400 MHz, CDCl₃) δ 9.03 (d, 1H), 8.83 (d, 1H), 8.54 (d, 1H), 8.14(m, 1H), 7.95 (d, 1H), 7.58 (br.s, 1H), 2.30 (s, 3H)

Example P3: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-N,2-dimethyl-propanamide(Compound C4)

Step 1: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-N,2-dimethyl-propanamide

To a stirred solution ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-2-methyl-propanamide(0.135 g, 0.4125 mmol) in DMF (9 mL) at 0° C. (ice bath) was addedsodium hydride (as a 60% dispersion in mineral oil) (0.017 g, 0.4331mmol) in a single portion. After 5 minutes the mixture was removed fromthe ice bath and stirred at ambient for a further 5 minutes. Thereaction was then re-cooled to 0° C. (ice bath) and iodomethane (0.027mL 0.4331 mmol) was added dropwise. After 10 minutes the mixture wasallowed to warm to ambient and stirred for a further 30 minutes. Themixture was quenched with 2M HCl (500 μL) and concentrated in vacuo. Theresulting residue was purified via flash column chromatography on silicagel using an EtOAc/isohexane gradient as eluent to give the desiredcompound (9 mg, 6%).

¹H NMR (400 MHz, CD₃OD, major rotamer) δ 9.18 (1H, s), 8.57 (1H, d),8.17 (1H, m), 8.12 (1H, d), 7.77 (1H, d), 3.18 (3H, s), 2.21 (1H, m),1.12 (3H, d), 0.97 (3H, d)

Example P4: Synthesis ofN-acetyl-N-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]acetamide(Compound C5)

Step 1: Synthesis ofN-acetyl-N-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]acetamide

To a stirred solution of6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridin-3-amine (0.2 g, 0.778mmol) in DCM (20 mL) was added pyridine (0.25 mL) followed by dropwiseaddition of acetyl chloride (0.067 mL, 0.93 mmol). The resultant paleyellow solution was left to stand at room temperature overnight. Thesolvent was removed in vacuo and the sample purified via flash columnchromatography on silica gel using an EtOAc/isohexane gradient aseluent. The crude material was further purified by mass-directed reversephase HPLC to give the desired compound (20.3 mg, 8%) ¹H NMR (400 MHz,CDCl₃) δ 9.08 (s, 1H), 8.61 (d, 1H), 8.18 (m, 1H), 8.08 (d, 1H), 7.72(d, 1H), 2.33 (s, 6H)

Example P5: Synthesis ofN-[6-(5-chloro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-N,2-dimethyl-propanamide(Compound C12)

Step 1: Synthesis of 6-chloro-2-(trifluoromethyl)pyridin-3-amine

To a stirred solution of tert-butylN-[6-chloro-2-(trifluoromethyl)-3-pyridyl]carbamate (2.5 g, 8.4 mmol) inDCM (8 mL) was added TFA (6.6 mL, 84 mmol). The reagents were stirredovernight at room temperature. The reaction was basified with saturatedaq sodium bicarbonate solution and then extracted with DCM (2×10 mL).The combined organic extracts were dried over MgSO₄ and concentrated togive the desired compound (1.50 g, 91%) as a waxy white solid.

¹H NMR (400 MHz, CDCl₃) δ 7.25 (d, 1H), 7.02 (d, 1H), 4.27 (br.s, 2H)

Step 2: Synthesis ofN-[6-chloro-2-(trifluoromethyl)-3-pyridyl]-2-methyl-propanamide

To a stirred solution of 6-chloro-2-(trifluoromethyl)pyridin-3-amine(351 mg, 1.79 mmol) in DCM (3 mL) and pyridine (0.58 mL, 7.14 mmol) wasadded 2-methylpropanoyl chloride (0.374 mL, 3.57 mmol). The reactionmixture was allowed to stir at room temperature overnight. The reactionmixture was concentrated and purified by flash chromatography on silicausing a gradient from 5-100% EtOAc in isohexane as eluent to give thedesired compound (234 mg, 49%) as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 8.73 (d, 1H), 7.58 (br.s, 1H), 7.51 (d, 1H),2.67-2.54 (m, 1H), 1.29 and 1.21 (2×d, 6H)

Step 3: Synthesis ofN-[6-(5-chloro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-N,2-dimethyl-propanamide

A microwave vial was charged withN-[6-chloro-2-(trifluoromethyl)-3-pyridyl]-2-methyl-propanamide (117 mg,0.44 mmol), (5-chloro-3-pyridyl)boronic acid (138 mg, 0.88 mmol),caesium carbonate (429 mg, 1.32 mmol),[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (32 mg,0.044 mmol), 1,4-dioxane (3 mL) and H₂O (0.3 mL). The vial was cappedand the contents degassed by evacuating and purging with nitrogen (×3).The reaction mixture was heated under microwave irradiation at 120° C.for 30 mins. The reaction mixture was concentrated and purified by flashchromatography on silica using a gradient from 5-100% EtOAc in isohexaneas eluent to give the desired compound (100 mg, 66%) as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 9.08 (s, 1H), 8.89 (d, 1H), 8.62 (s, 1H), 8.38(s, 1H), 7.96 (d, 1H), 7.68 (br s, 1H), 2.69-2.59 (m, 1H), 1.32 (d, 6H)

Example P6: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-N-methyl-propanamide(Compound C15)

Step 1: Synthesis of tert-butylN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-N-methyl-carbamate

To a stirred solution of tert-butylN-[6-pyrimidin-5-yl-2-(trifluoromethyl)-3-pyridyl]carbamate (422 mg,1.24 mmol) in DMF (4.2 mL) at 5° C. under an N₂ atmosphere was addedsodium hydride (as a 60% dispersion in mineral oil) (0.059 g, 1.49 mmol)in a single portion. The reaction mixture was allowed to warm to roomtemperature and stir for 1 hr then iodomethane (0.115 mL, 1.86 mmol) wasadded and the reaction mixture stirred for a further 2 hrs. The reactionmixture was diluted with water and extracted with EtOAc (3×10 mL). Thecombined organic extracts were washed with brine, dried over MgSO₄ andconcentrated to give a yellow gum. The crude product was purified byflash chromatography on silica using a gradient from 5-100% EtOAc inisohexane as eluent to give the desired compound (354 mg, 81%) as anorange gum.

¹H NMR (400 MHz, CDCl₃, major rotamer) δ 9.07 (s, 1H), 8.57 (d, 1H),8.20 (br.d, 1H), 8.01 (d, 1H), 7.76 (d, 1H), 3.22 (s, 3H), 1.33 (s, 9H)

Step 2: Synthesis of6-(5-fluoro-3-pyridyl)-N-methyl-2-(trifluoromethyl)pyridin-3-amine

To a stirred solution of tert-butylN-methyl-N-[6-pyrimidin-5-yl-2-(trifluoromethyl)-3-pyridyl]carbamate(453 mg, 1.28 mmol) in DCM (10 mL) was added portionwise,trifluoroacetic acid (0.49 mL, 6.39 mmol). The reaction mixture wasstirred at room temperature for 72 h. The reaction mixture was dilutedwith DCM and saturated sodium bicarbonate solution was addedportionwise. The two layers were separated and the aqueous extractedagain with DCM (×2). The organics were combined, washed with brine,dried over MgSO₄ and concentrated. The crude product was purified byflash chromatography on silica using a gradient from 0-10% MeOH in DCMas eluent to give the desired compound (317 mg, 98%) as a yellow solid.

¹H NMR (400 MHz, CDCl₃) δ 8.93 (s, 1H), 8.42 (d, 1H), 8.05 (m, 1H), 7.82(d, 1H), 7.17 (d, 1H), 4.72 (br.s, 1H), 2.98 (app. d, 3H)

Step 3: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]-N-methyl-propanamide

To a stirred solution of6-pyrimidin-5-yl-2-(trifluoromethyl)pyridin-3-amine (80 mg, 0.33 mmol)in 1,4-dioxane (3 mL) was added pyridine (0.03 mL, 0.4 mmol) and thenpropionyl chloride (0.035 mL, 0.4 mmol). The reaction was stirred atroom temperature overnight. The reaction mixture was concentrated andtaken up in ethyl acetate and washed with water, saturated sodiumbicarbonate solution and then water. The organic phase was dried overMgSO₄, concentrated and then purified by mass-directed reverse phaseHPLC to give the desired compound (36 mg, 19%) as an oil.

¹H NMR (400 MHz, CDCl₃, major rotamer) δ 9.15 (s, 1H), 8.64 (m, 1H),8.39 (m, 1H), 8.15 (d, 1H), 7.86 (d, 1H), 3.27 (s, 3H), 2.00 (2H, m),1.08 (3H, t)

Example P7: Synthesis of2-methyl-N-(2-methyl-6-pyrimidin-5-yl-3-pyridyl)propanamide (CompoundC2)

Step 1: Synthesis of tert-butyl N-(6-chloro-2-methyl-3-pyridyl)carbamate

To stirred solution of 6-chloro-2-methyl-pyridine-3-carboxylic acid intert-butanol (15 mL) was added Et₃N (1.85 mL, 13.3 mmol) and DPPA (2.86mL, 3.3 mmol) and the reaction heated at 90° C. for 2 hours. Thereaction was allowed to cool to room temperature overnight, diluted withwater (50 mL) and extracted with EtOAc (3×30 mL). The combined organicextracts were washed with water (15 mL), brine (15 mL), dried over MgSO₄and evaporated to dryness under reduced pressure. The residue waspurified by flash chromatography over SiO₂ using a gradient of 5-50%EtOAc/isohexane as eluent to give the desired product (1.75 g, 71%) as awhite solid.

¹H NMR (400 MHz, CDCl₃) δ 8.18 (br. d, 1H), 7.16 (d, 1H), 6.26 (br.d,1H), 2.48 (s, 3H), 1.52 (s, 9H).

Step 2: Synthesis of 6-chloro-2-methyl-pyridin-3-amine

To a stirred solution of tert-butylN-(6-chloro-2-methyl-3-pyridyl)carbamate (500 mg, 2.06 mmol) in DCM (8mL) was added trifluoroacetic acid (1.63 mL, 20.6 mmol). The reactionwas heated at reflux for 2 hours, cooled to RT and quenched withsaturated aqueous NaHCO₃ solution (20 mL). The reaction mixture wasextracted with DCM (3×20 mL) and the combined organic extracts driedover MgSO₄ and evaporated to dryness under reduced pressure to give thedesired product (320 mg, quant) as a waxy solid.

¹H NMR (400 MHz, CDCl₃) δ 6.89 (d, 1H), 6.81 (d, 1H), 3.59 (br.s, 2H),2.29 (s, 3H).

Step 3: Synthesis ofN-(6-chloro-2-methyl-3-pyridyl)-2-methyl-propanamide

To a stirred solution of 6-chloro-2-methyl-pyridin-3-amine (320 mg, 2.24mmol) in DCM (3 mL) was added pyridine (0.726 mL, 8.98 mmol) and2-methyl propionyl chloride (0.47 mL, 4.49 mmol). The reaction wasstirred at room temperature overnight, then evaporated to dryness underreduced pressure and the residue purified by flash chromatography overSiO₂ using an EtOAc/isohexane gradient as eluent to give the desiredproduct (259 mg, 54%) as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 8.27 (d, 1H), 7.19 (d, 1H, 6.93 (br.s, 1H),2.61-2.54 (m, 1H), 2.49 (s, 3H), 1.29 (d, 6H).

Step 4: Synthesis of2-methyl-N-(2-methyl-6-pyrimidin-5-yl-3-pyridyl)propanamide

To a solution of N-(6-chloro-2-methyl-3-pyridyl)-2-methyl-propanamide(130 mg, 0.611 mmol) in EtOH (10 mL) was added pyrimidin-5-yl boronicacid (114 mg, 0.92 mmol), K₂CO₃ (188 mg, 1.34 mmol) and[Pd(IPr*)(cin)Cl] (36 mg, 0.03 mmol). The reaction was heated at refluxfor 2 hours, allowed to cool to room temperature and evaporated todryness under reduced pressure. The residue was purified by flashchromatography over SiO₂ using an EtOAc/isohexane gradient as eluent togive the desired product (146 mg, 93%) as an off-white solid.

¹H NMR (400 MHz, CDCl₃) δ 9.30 (s, 2H), 9.22 (s, 1H), 8.50 (d, 1H), 7.63(d, 1H), 7.08 (br.s, 1H), 2.68-2.58 (m, 1H), 2.62 (s, 3H), 1.32 (d, 6H).

Example P8: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]pyridine-3-carboxamide(Compound C50)

Step 1: Synthesis of3-chloro-6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridine

A suspension of 3,6-dichloro-2-(trifluoromethyl)pyridine (2.0 g, 9.26mmol) and (5-fluoro-3-pyridyl) boronic acid (1.44 g, 10.19 mmol) in amixture of EtOH (5.4 mL), toluene (20 mL) and water (9.25 mL) wassparged with N₂ for 30 minutes at RT. K₂CO₃ (2.56 g, 18.52 mmol) andXantphos Pd G4 (222 mg, 0.232 mmol) was added and the reaction heated to80° C. for 2.5 hours. The reaction was allowed to cool to RT, dilutedwith EtOAc (100 mL) and washed with water (100 mL). The aqueous phasewas extracted with further EtOAc (2×100 mL). The combined organicextracts were dried over MgSO₄ and evaporated to dryness under reducedpressure. The crude material was purified by flash chromatography onsilica gel using an EtOAc/isohexane gradient as eluent to give thedesired product (2.16 g, 84%) as a pale orange oil which solidified onstanding.

¹H NMR (400 MHz, CDCl₃) δ 9.03 (s, 1H), 8.58 (s, 1H), 8.15 (d, 1H), 7.98(d, 1H), 7.92 (d, 1H).

Step 2: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]pyridine-3-carboxamide(Compound C50)

A microwave vial was charged with3-chloro-6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridine (50 mg, 0.18mmol), tBuBrettPhos Pd G3 (6 mg, 0.0072 mmol), K₃PO₄ (54 mg, 0.25 mmol),pyridine-3-carboxamide (26 mg, 0.22 mmol) and ^(t)BuOH (1 mL) and heatedfor 1 hour at 130° C. under microwave irradiation. The reaction wasdiluted with EtOAc (20 mL) and washed with water (20 mL). The aqueouslayer was extracted with further EtOAc (2×20 mL) and then the combinedorganic extracts were dried over MgSO₄ and evaporated to dryness underreduced pressure to give an orange oil. The crude product was purifiedby flash chromatography on silica gel using an EtOAc/isohexane gradientas eluent to give the desired compound (30 mg, 46%) as a colourlesssolid.

¹H NMR (400 MHz, CDCl₃) δ 9.16 (s, 1H), 9.10-9.00 (m, 2H), 8.91-8.87 (m,1H), 8.56 (d, 1H), 8.48 (br. s, 1H), 8.25-8.20 (m, 1H), 8.20-8.13 (m,1H), 8.07 (d, 1H), 7.56-7.50 (m, 1H).

Example P9: Synthesis of1-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]piperidin-2-one(Compound C54)

Step 1: Synthesis of1-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]piperidin-2-one(Compound C54)

A microwave vial was charged with3-chloro-6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridine (150 mg,0.54 mmol), JackiePhos Pd G3 (25 mg, 0.022 mmol), Cs₂CO₃ (353 mg, 1.08mmol) piperidin-2-one (134 mg, 1.36 mmol) and toluene (1.5 mL) andheated for 1 hour at 150° C. under microwave irradiation. The reactionmixture was diluted in EtOAc (20 mL) and washed with water (20 mL). Theaqueous layer was extracted with further EtOAc (2×20 mL) and thecombined organic extracts were dried over MgSO₄ and evaporated todryness under reduced pressure. The crude product was purified by flashchromatography on silica gel using an EtOAc/isohexane gradient aseluent. The resultant pale brown solid was triturated with water andfiltered through a plug of celite, washing with further water. The plugwas then eluted with DCM and the eluant dried over MgSO₄ and evaporatedto dryness under reduced pressure to give the desired product (25 mg,14%) as a pale orange solid.

¹H NMR (400 MHz, CDCl₃) δ 9.03 (s, 1H), 8.57 (s, 1H), 8.17 (d, 1H), 8.04(d, 1H), 7.80 (d, 1H), 3.66-3.53 (m, 2H), 2.17-2.53 (m, 2H), 2.11-1.90(m, 4H).

Example P10: Synthesis of1-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]pyrrolidine-2,5-dione(Compound C67)

Step 1: Synthesis of Synthesis of1-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]pyrrolidine-2,5-dione(Compound C67)

To a stirred solution of6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridin-3-amine (1.0 g, 3.9mmol) in DCM (250 mL) was added Et₃N (1.3 mL, 9.2 mmol) and dropwisesuccinyl chloride (1.3 mL, 11.0 mmol). The reaction was stirred at RTfor 4 hours and then evaporated to dryness under reduced pressure. Thecrude material was purified initially by flash chromatography on silicagel using a MeOH/DCM gradient as eluent and subsequently bymass-directed reverse phase HPLC to give the desired product (395 mg,30%) as a tan solid.

¹H NMR (400 MHz, CDCl₃) 9.46 (s, 2H), 9.28 (s, 1H), 8.05 (d, 1H), 7.78(d, 1H), 3.15-2.87 (m, 4H).

Example P11: Synthesis ofN-[2-cyano-6-(5-fluoro-3-pyridyl)-3-pyridyl]-2-methoxy-acetamide(Compound C114)

Step 1: Synthesis of3-amino-6-(5-fluoro-3-pyridyl)pyridine-2-carbonitrile

A mixture of 3-amino-6-chloro-pyridine-2-carbonitrile (330 mg, 2.15mmol), 5-fluoropyridine-3-boronic acid (394 mg, 2.69 mmol), potassiumcarbonate (633 mg, 4.73 mmol) and [Pd(IPr*)(cin)Cl) (126 mg, 0.11 mmol)in EtOH (9.9 mL) was heated at 80° C. for 1 hour under an N₂ atmosphereand then allowed to cool to room temperature. The mixture was filteredthrough celite and concentrated in vacuo. The resultant orange-brown gumwas adsorbed onto silica and purified by flash chromatography on silicausing an EtOAc/isohexane gradient as eluent to give the desired product(80 mg, 17%) as a brown gum.

¹H NMR (400 MHz, CD₃OD) δ 8.95 (d, 1H), 8.43 (d, 1H), 8.18-8.09 (m, 1H),7.93 (d, 1H), 7.35 (d, 1H)

Step 2: Synthesis ofN-[2-cyano-6-(5-fluoro-3-pyridyl)-3-pyridyl]-2-methoxy-acetamide(Compound C114)

To a stirred solution of3-amino-6-(5-fluoro-3-pyridyl)pyridine-2-carbonitrile (0.2 g, 0.93 mmol)and pyridine (0.30 ml. 3.73 mmol) in DCM (3 mL) at 0° C. was addeddropwise a solution of 2-methoxyacetyl chloride (0.127 g, 1.17 mmol) inDCM (2 mL). The reaction was allowed to warm to RT and stirred for afurther hour. The reaction was evaporated to dryness under reducedpressure and purified twice by flash chromatography on silica gel usingEtOAc/isohexane gradients as eluent to give the desired compound (126mg, 47%).

¹H NMR (400 MHz, CDCl₃) δ 9.12 (br. s, 1H), 9.02 (s, 1H), 9.00 (d, 1H),8.55 (d, 1H), 8.09 (m, 1H), 8.00 (d, 1H), 4.13 (s, 2H), 3.60 (s, 3H)

Example P12: Synthesis ofN-acetyl-N-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]propanamide(Compound C121)

Step 1: Synthesis ofN-acetyl-N-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]propanamide(Compound C121)

To a stirred solution ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]propanamide (0.1g, 0.32 mmol) in THF (15 mL) at 0° C. under an N₂ atmosphere was addedNaHMDS (1M in THF) (0.32 mL, 0.3193 mmol) and the mixture stirred forca. 5 mins. After this time acetyl chloride (0.05 mL, 0.7024 mmol) wasadded and the mixture stirred at 0° C. for a further hour then allowedto warm to RT over 3 hours. 10% Sodium metabisulphite (10 mL) was addedand the mixture was stirred for ca. 5 mins. The material wasconcentrated under reduced pressure to remove most of the THF and themixture was diluted with DCM (50 mL) and passed through aphase-separation cartridge. The resulting solution was evaporated todryness under reduced pressure and the crude material purified twice byflash chromatography on silica gel using EtOAc/isohexane gradients aseluent to give the desired compound (5 mg, 4%) as a colourless gum.

¹H NMR (400 MHz, CDCl₃) δ 9.08 (t, 1H), 8.60 (d, 1H), 8.21 (m, 1H), 8.11(d, 1H), 7.77 (d, 1H), 2.52 (m, 1H), 2.40 (s, 3H), 1.14 (t, 3H).

Example P13: Synthesis of4-[[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]amino]-4-oxo-butanoicacid (Compound C113)

Step 1: Synthesis of4-[[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]amino]-4-oxo-butanoicacid (Compound C113)

To a stirred solution of1-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]pyrrolidine-2,5-dione(0.1 g, 0.29 mmol) in THF (2 mL) was added NaOH (2M in H₂O) (0.5 mL) andthe mixture stirred at RT for 5 hours. The reaction mixture wasevaporated to dryness under reduced pressure and stored at -20° C.overnight. The residue was purified by mass-directed reverse phase HPLCto give the desired product (16 mg, 15%) as a colourless solid.

¹H NMR (400 MHz, CD₃OD) 9.14 (dd, 1H), 8.55 (d, 1H), 8.32-8.24 (m, 3H),2.75 (m, 2H), 2.70 (m, 2H).

Example P14: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]pyrimidine-5-carboxamide(Compound C120)

Step 1: Synthesis ofN-[6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)-3-pyridyl]pyrimidine-5-carboxamide(Compound C120)

To a solution of6-(5-fluoro-3-pyridyl)-2-(trifluoromethyl)pyridin-3-amine (80 mg, 0.31mmol) and pyrimidine-5-carboxylic acid (116 mg, 0.93 mmol) in toluene(3.1 mL) was added sequentially N,N-diisopropylethylamine (0.27 mL, 1.56mmol) and then 1-propanephosphonic anhydride (50% solution in EtOAc)(790 mg, 1.24 mmol). The reaction was heated at reflux for 18 hours,cooled to RT and the poured into sat. aq. NaHCO₃ solution (20 mL). Thereaction was extracted with DCM (2×10 mL), the combined organic extractswere evaporated to dryness under reduced pressure and the residuepurified by mass-directed reverse phase HPLC to give the desired product(90 mg, 80%) as a white solid).

¹H NMR (400 MHz, CDCl₃) δ 9.48 (s, 1H), 9.27 (s, 2H), 9.09 (t, 1H), 9.00(d, 1H), 8.59 (d, 1H), 8.33 (br. s, 1H), 8.25-8.17 (m, 1H), 8.10 (d,1H).

Further examples of the invention were made in an analogous manner usingthe methods described above in Examples P1 to P14, with respect tocompounds C2, C4, C5, C9, C10, C12, C15, C50, C54, C67, C114, C121, C113and C120. Table 2 below, shows the structure of these compounds and thephysical characterising data obtained using one or more of methods A toC as outlined below.

TABLE 2 Characterising data for Compounds of formula (I) made by themethods described above ¹H NMR Data Cmpd (400 MHz, CDCl₃ Mass/ Mass m/zID Structure unless stated) Da Spec Method C1

9.02 (s, 1H), 8.52 (d, 1H), 8.18-8.12 (m, 1H), 7.71 (d, 1H), 7.49 (d,1H), 3.10-2.98 (m, 2H), 2.48 (s, 3H), 1.19 (d, 12H) 343.2 — — C2

9.30 (s, 2H), 9.22 (s, 1H), 8.50 (d, 1H), 7.63 (d, 1H), 7.08 (br.s, 1H),2.68-2.58 (m, 1H), 2.62 (s, 3H), 1.32 (d, 6H) 256.1 — — C3

8.99 (s, 1H), 8.49- 8.42 (m, 2H), 8.10-8.04 (m, 1H), 7.63 (d, 1H), 7.14(br.s, 1H), 2.69- 2.59 (m, 1H), 2.60 (s, 3H), 1.31 (d, 6H) 273.1 — — C4

(CD₃OD, major rotamer) 9.18 (1H, s), 8.57 (1H, d), 8.17 (1H, m), 8.12(1H, d), 7.77 (1H, d), 3.18 (3H, s), 2.21 (1H, m), 1.12 (3H, d), 0.97(3H, d) 341.1 [MH]+ 342; tr 0.91 mins B C5

9.08 (s, 1H), 8.61 (d, 1H), 8.18 (m, 1H), 8.08 (d, 1H), 7.72 (d, 1H),2.33 (s, 6H); 341.1 — — C6

9.42 (s, 2H), 9.32 (s, 1H), 8.10 (d, 1H), 7.78 (d, 1H), 2.34 (s, 6H);324.1 — — C7

9.35 (s, 2H), 9.30 (s, 1H), 8.91 (d, 1H), 7.95 (d, 1H), 7.60 (br.s, 1H),2.32 (s, 3H) 282.1 — — C8

9.34 (s, 2H), 9.24 (s, 1H), 8.92 (d, 1H), 7.95 (d, 1H), 7.70 (br.s, 1H),2.59 (m, 1H), 1.32 (d, 6H) 310.1 — — C9

9.03 (d, 1H), 8.83 (d, 1H), 8.54 (d, 1H), 8.14 (m, 1H), 7.95 (d, 1H),7.58 (br.s, 1H), 2.30 (s, 3H); 299.1 — — C10

9.07 (br.s, 1H), 8.78 (d, 1H), 8.52 (1H, br. s), 8.12 (m, 1H), 7.92 (d,1H), 7.67 (br.s, 1H), 2.58 (m, 1H), 1.31 (d, 6H) 327.1 — — C11

9.39 (s, 1H), 8.97 (d, 1H), 8.92 (d, 1H), 8.66 (d, 1H), 8.00 (d, 1H),7.71 (br.s, 1H), 2.69- 2.59 (m, 1H), 1.31 (d, 6H) 334.1 — — C12

9.08 (d, 1H), 8.89 (d, 1H), 8.62 (d, 1H), 8.38 (d, 1H), 7.96 (d, 1H),7.68 (br.s, 1H), 2.69- 2.59 (m, 1H), 1.32 (d, 6H) 343.1 — — C13

9.10 (s, 1H), 8.90 (d, 1H), 8.55 (d, 1H), 8.15 (d, 1H), 8.00 (d, 1H),7.61 (br.s, 1H), 2.51 (q, 2H), 1.30 (t, 3H) 313.1 — — C14

9.15 (m, 2H), 8.55 (d, 1H), 8.50 (s, 1H), 8.15 (d, 1H), 8.05 (d, 1H),7.90 (m, 2H), 7.65- 7.52 (m, 3H) 361.1 — — C15

(major rotamer) 9.15 (s, 1H), 8.64 (m, 1H), 8.39 (m, 1H), 8.15 (d, 1H),7.86 (d, 1H), 3.27 (s, 3H), 2.00 (2H, m), 1.08 (3H, t) 327.1 [MH]+ 328;tr 1.95 min A C16

(CD₃OD, major rotamer) 9.21 (s, 1H), 8.83 (d, 1H), 8.40 (m, 2H), 8.06(d, 1H), 5.93 (m, 1H), 5.23 (d, 1H), 5.15 (dd, 1H), 4.90 (m, 1H), 3.65(dd, 1H), 2.20 (m, 1H), 1.05 (d, 3H), 1.03 (d, 3H) 367.1 [MH]+ 368; tr0.74 mins C C17

9.45 (d, 2H), 9.30 (s, 1H), 9.15 (d, 1H), 8.47 (br. s, 1H), 8.05 (d,1H), 7.90 (d, 2H), 7.65- 7.52 (m, 3H) 344.1 — — C18

9.40 (s, 2H), 9.30 (s, 1H), 8.90 (d, 1H), 7.94 (d, 1H), 7.65 (br. s,1H), 2.50 (q, 2H), 1.30 (t, 3H) 296.1 — — C19

9.03 (s, 1H), 8.90 (d, 1H), 8.53 (d, 1H), 8.13 (m, 1H), 7.98 (d, 1H),7.59 (br.s, 1H), 2.34 (d, 2H), 1.90 (m, 1H), 1.84-1.68 (m, 5H),1.38-1.01 (m, 5H) 381.1 [MH]+ 382; tr 0.82 mins C C20

367.1 [MH]+ 368; tr 0.77 mins C C21

9.03 (s, 1H), 8.91 (d, 1H), 8.53 (d, 1H), 8.12 (d, 1H), 7.98 (d, 1H),7.57 (br.s, 1H), 3.28 (m, 1H), 2.46-2.31 (4H, m), 2.13-1.93 (2H, m)339.1 [MH]+ 340; tr 0.65 mins C C22

9.03 (d, 1H), 8.91 (d, 1H), 8.52 (d, 1H), 8.12 (m, 1H), 7.92 (d, 1H),7.58 (br. s, 1H), 2.47 (t, 2H), 1.81 (m, 2H), 1.07 (t, 3H) 327.1 — — C23

9.04 (s, 1H), 8.99 (d, 1H), 8.54 (d, 1H), 8.14 (m, 1H), 8.00 (d, 1H),7.62 (br.s, 1H), 7.09 (m, 1H), 6.05 (dd, 1H), 2.01 (dd, 3H) 325.1 — —C24

9.42 (br. s, 1H), 9.04 (s, 1H), 8.94 (d, 1H), 8.52 (d, 1H), 8.08 (m,1H), 7.93 (d, 1H), 3.72 (t, 2H), 3.51 (s, 3H), 2.72 (t, 2H) 343.1 — —C25

9.03 (1H, app. dd), 8.93 (1H, d), 8.52 (1H. d), 8.11 (1H, m), 7.94 (1H,d), 7.58 (br. s, 1H), 2.48 (2H, app. t), 1.88-1.72 (3H, m), 1.68-1.55(2H, m), 1.49-1.55 (2H, m), 1.07-1.16 (2H, m) 367.1 — — C26

9.07 (s, 1H), 8.82 (m, 2H), 8.56 (d, 1H), 8.17 (dd, 1H), 8.05 (d, 1H),6.13 (s, 1H) 367.0 — — C27

9.12-8.93 (m, 3H), 8.52 (d, 1H), 8.12 (m, 1H), 7.96 (d, 1H), 4.11 (s,2H), 3.56 (s, 3H) 329.1 — — C28

(major rotamer) 9.25 (br.s, 1H), 9.05 (d, 1H), 9.02 (s, 1H), 8.55 (d,1H), 8.15 (m, 1H), 8.05 (d, 1H), 7.43 (m, 2H), 7.15 (m, 1H), 6.92 (m,2H), 4.68 (s, 2H) 391.1 [MH]+ 392; tr 0.77 mins C C29

9.05 (s, 1H), 9.01 (s, 1H), 8.78 (d, 1H), 8.58 (s, 1H), 8.12-8.03 (m,2H) 401.0 [MH]+ 402; tr 0.74 mins C C30

9.11-9.06 (m, 2H), 8.55 (s, 1H), 8.42 (s, 1H), 8.15 (dd, 1H), 8.03 (d,1H), 7.80 (d, 2H), 7.35 (d, 2H), 2.45 (s, 3H) 375.1 [MH]+ 376; tr 0.74mins C C31

397.1 [MH]+ 398; tr 0.66 mins C C33

9.15 (br. d, 1H), 9.07 (s, 1H), 9.05 (d, 1H), 8.55 (d, 1H), 8.15 (dd,1H), 8.10-8.05 (m, 2H), 7.15 (m, 1H) 415.1 C34

9.05 (s, 1H), 8.80 (d, 1H), 8.55 (s, 1H), 8.15 (dd, 1H), 8.05 (m, 2H),1.35 (s, 9H) 341.1 C35

9.15 (s, 1H), 9.05 (br. s, 1H), 8.80 (d, 1H), 8.55 (s, 1H), 8.15 (dd,1H), 8.05 (d, 1H), 4.30 (s, 2H) 333.0 C36

9.10 (s, 1H), 8.95 (d, 1H), 8.55 (m, 2H), 8.15 (dd, 1H), 8.05 (d, 1H),2.20 (s, 3H), 1.75 (s, 6H) 385.1 C37

9.05 (s, 1H), 9.00 (d, 1H), 8.55 (s, 1H), 8.25 (dd, 1H), 8.05 (d, 1H),7.55 (br. s, 1H), 5.75 (s, 1H), 2.30 (s, 3H), 2.00 (s, 3H) 339.1 C38

9.15 (s, 1H), 8.65 (s, 1H), 8.35 (d, 1H), 8.10 (d, 1H), 7.80 (d, 1H),6.00 (s, 2H), 2.15 (s, 6H), 1.90 (s, 6H) 421.1 C39

353.1 [MH]+ 354; tr 0.70 mins C C42

11.20 (s, 1H), 9.05 (s, 1H), 8.90 (d, 1H), 8.55 (d, 1H), 8.15 (dd, 1H),8.05 (d, 1H), 4.40 (q, 2H), 3.55 (s, 2H), 1.35 (t, 3H) 371.1 C44

9.08 (s, 1H), 8.59 (d, 1H), 8.24-8.19 (m, 1H), 8.11 (d, 1H), 7.78 (d,1H), 2.50 (q, 4H), 1.15 (t, 6H) 369.1 C45

(CD₃OD) 9.20 (s, 1H), 9.15 (s, 1H), 8.80 (d, 1H), 8.60 (d, 1H), 8.40 (m,3H), 8.30 (d, 1H), 7.65 (m, 1H) 362.1 C46

9.25 (br, 1H), 9.10 (m, 2H), 8.55 (br. s, 1H), 8.25 (t, 1H), 8.15 (dd,1H), 8.05 (d, 1H), 7.70 (m, 1H), 7.40 (t, 1H), 7.25 (t, 1H) 379.1 C47

9.05 (m, 2H), 8.55 (s, 1H), 8.3 (br. s, 1H), 8.20 (dd, 1H), 8.05 (d,1H), 7.65 (m, 2H), 7.20 (m, 1H) 367.0 C49

9.10 (s, 1H), 8.95 (d, 1H), 8.55 (d, 1H), 8.15 (dd, 1H), 8.05 (d, 1H),7.60 (br. s, 1H), 2.45 (t, 2H), 1.75 (m, 2H), 1.45 (m, 2H), 1.00 (t, 3H)341.1 C50

9.16 (s, 1H), 9.10- 9.00 (m, 2H), 8.91-8.87 (m, 1H), 8.56 (d, 1H), 8.48(br s, 1H), 8.25- 8.20 (m, 1H), 8.20-8.13 (m, 1H), 8.07 (d, 1H), 7.56-7.50 (m, 1H). 362.1 C51

9.05 (m, 2H), 8.55 (s, 1H), 8.20 (m, 2H), 8.05 (d, 1H), 7.45 (d, 1H),7.00 (d, 1H), 2.60 (s, 3H) 381.1 C52

9.05 (m, 2H), 8.55 (s, 1H), 8.20 (m, 2H), 8.05 (d, 1H), 7.45 (d, 1H),6.85 (d, 1H) 2.60 (s, 3H) 381.1 C53

9.40 (br. s, 1H), 9.05 (s, 1H), 8.90 (d, 1H), 8.55 (s, 1H), 8.15 (dd,1H), 7.90 (d, 1H), 2.50 (t, 2H), 1.90- 1.75 (m, 4H), 1.70-1.50 (m, 5H),1.15 (m, 2H) 381.1 C54

9.03 (s, 1H), 8.57 (s, 1H), 8.17 (d, 1H), 8.04 (d, 1H), 7.80 (d, 1H),3.66- 3.53 (m, 2H), 2.17-2.53 (m, 2H), 2.11-1.90 (m, 4H) 339.1 C55

9.03 (s, 1H), 8.58 (s, 1H), 8.17 (d, 1H), 8.03 (d, 1H), 7.83 (d, 1H),3.80 (t, 2H), 2.61 (t, 2H), 2.31 (quintet, 2H). 325.1 C56

(CD₃OD) 9.13 (br, 1H), 8.56 (br. s, 1H), 8.39-8.27 (m, 2H), 8.22 (d,1H), 3.51 (q, 2H) 367.1 C57

(CD₃OD) 9.21 (s, 1H), 8.62 (d, 1H), 8.48 (d, 1H), 8.44- 8.35 (m, 1H),8.21 (d, 1H), 4.99 (d, 1H), 4.35 (d, 1H), 2.19-1.99 (m, 2H), 1.06 (t,3H) 352.1 C58

(CD₃OD) 9.12 (s, 1H), 8.62 (d, 1H), 8.29-8.13 (m, 2H), 8.08 (d, 1H),5.35 (d, 1H), 3.88 (d, 1H), 2.33-2.19 (m, 1H), 1.18-1.01 (m, 6H) 366.1C59

9.05 (s, 1H), 8.90 (d, 1H), 8.55 (s, 1H), 8.15 (d, 1H), 7.9 (s, 1H),7.80 (bs, 1H), 1.60 (m, 1H), 1.15 (m, 2H), 0.95 (m, 2H) 325.1 C60

9.42 (s, 2H), 9.31 (s, 1H), 8.97 (br. s, 1H), 8.79 (d, 1H), 8.03 (d, 1H)384.0 C61

9.12 (s, 1H), 8.61 (d, 1H), 8.32-8.24 (m, 1H), 8.16 (d, 1H), 8.03 (d,1H), 5.23 (dd, 1H), 3.79 (dd, 1H), 2.31-2.27 (m, 1H), 2.27-2.16 (m, 1H),1.08 (dd, 6H) 365.1 C62

9.01 (s, 1H), 8.51 (d, 1H), 8.19-8.12 (m, 1H), 7.90 (d, 1H), 7.30-7.22(m, 1H), 6.02 (tt, 1H), 4.41 (t, 2H), 2.41- 2.26 (m, 2H), 2.19 (q, 2H),1.12 (t, 3H) 391.1 C63

369.1 [MH]+ 370; tr 0.61 mins C C65

9.43 (s, 2H), 9.31 (s, 1H), 8.92 (br. s, 1H), 8.81 (d, 1H), 8.02 (d,1H), 6.17 (s, 1H) 350.0 C66

9.05 (s, 1H), 9.00 (d, 1H), 8.57 (br.s, 1H), 8.53 (d, 1H), 8.16 (m, 1H),8.00 (d, 1H), 2.45 (d, 2H), 1.08 (m, 1H), 0.83 (m, 2H), 0.38 (m, 2H)339.1 C67

(CD₃OD) 9.19 (s, 1H), 8.62 (d, 1H), 8.45 (d, 1H), 8.41- 8.31 (m, 1H),8.05 (d, 1H), 2.97 (app. s, 4H) 339.1 C68

9.07 (s, 1H), 8.60 (d, 1H), 8.20 (m, 1H), 8.10 (d, 1H), 7.88 (br. s,1H), 3.70 (br. s, 3H) 415.0 C69

440.2 [MH]+ 441; tr 1.01 mins A C70

404.1 [MH]+ 405; tr 0.90 mins A C71

398.1 [MH]+ 399; tr 1.07 mins A C72

425.1 [MH]+ 426; tr 1.40 mins A C73

381.1 [MH]+ 382; tr 1.42 mins A C74

474.2 [MH]+ 475; tr 0.99 mins A C75

417.1 [MH]+ 418; tr 1.49 mins A C76

461.2 [MH]+ 462; tr 1.67 mins A C77

485.1 [MH]+ 486; tr 1.57 mins A C78

492.0 [MH]+ 493; tr 1.45 mins A C79

385.1 [MH]+ 386; tr 1.27 mins A C80

383.1 [MH]+ 384; tr 1.21 mins A C81

429.2 [MH]+ 430; tr 1.47 mins A C82

453.1 [MH]+ 454; tr 1.40 mins A C83

460.0 [MH]+ 461; tr 1.25 mins A C84

414.1 [MH]+ 415; tr 0.97 mins A C85

385.1 [MH]+ 386; tr 1.27 mins A C86

383.2 [MH]+ 384; tr 1.46 mins A C87

381.1 [MH]+ 382; tr 1.40 mins A C88

401.1 [MH]+ 402; tr 1.39 mins A C89

427.2 [MH]+ 428; tr 1.65 mins A C90

369.1 [MH]+ 370; tr 1.36 mins A C91

451.1 [MH]+ 452; tr 1.57 mins A C92

458.1 [MH]+ 459; tr 1.46 mins A C93

395.2 [MH]+ 396; tr 1.48 mins A C94

351.1 [MH]+ 352; tr 1.24 mins A C95

426.2 [MH]+ 427; tr 0.94 mins A C96

371.1 [MH]+ 372; tr 1.18 mins A C97

369.1 [MH]+ 370; tr 1.39 mins A C98

387.1 [MH]+ 388; tr 1.32 mins A C99

413.2 [MH]+ 414; tr 1.59 mins A C100

355.1 [MH]+ 356; tr 1.28 mins A C101

437.1 [MH]+ 438; tr 1.51 mins A C102

444.0 [MH]+ 445; tr 1.39 mins A C103

415.1 [MH]+ 416; tr 1.41 mins A C104

435.1 [MH]+ 436; tr 1.40 mins A C105

446.1 [MH]+ 447; tr 1.17 mins A C106

397.1 [MH]+ 398; tr 1.30 mins A C107

412.2 [MH]+ 413; tr 1.15 mins A C108

367.1 [MH]+ 368; tr 1.32 mins A C109

9.33 (s, 2H), 9.26 (s, 1H), 8.92 (d, 1H), 7.94 (d, 1H), 7.82 (br.s, 1H),1.58 (m, 1H), 1.18 (m, 2H), 0.94 (m, 2H) 308.1 C110

9.46 (s, 2H), 9.28 (s, 1H), 8.05 (d, 1H), 7.78 (d, 1H), 3.15-2.87 (m,4H) 322.1 C111

9.03 (t, 1H), 8.90 (d, 1H), 8.53 (d, 1H), 8.15-8.10 (m, 1H), 7.97 (d,1H), 7.66 (br. s, 1H), 2.81 (t, 1H), 2.10-1.98 (m, 2H), 1.97-1.87 (m,2H), 1.85- 1.77 (m, 2H), 1.69 (br. dd, 2H) 353.1 C112

8.98 (s, 1H), 8.89 (d, 1H), 8.52-8.46 (m, 2H), 8.11-8.04 (m, 1H), 7.92(d, 1H), 7.70-7.63 (m, 1H) 285.1 C113

(CD₃OD) 9.14 (dd, 1H), 8.55 (d, 1H), 8.32-8.24 (m, 3H), 2.75 (m, 2H),2.70 (m, 2H) 357.1 C114

9.12 (br. s, 1H), 9.02 (s, 1H), 9.00 (d, 1H), 8.55 (d, 1H), 8.09 (m,1H), 8.00 (d, 1H), 4.13 (s, 2H), 3.60 (s, 3H) 286.1 C115

(CD₃OD) 9.08 (s, 1H), 8.55 (d, 1H), 8.34-8.25 (m, 3H), 2.54 (q, 2H),1.25 (t, 3H) 270.1 C116

(CD₃OD) 9.41 (s, 2H), 9.22 (s, 1H), 8.39 (d, 1H), 8.28 (d, 1H), 2.57 (q,2H), 1.25 (t, 3H) 253.1 C117

9.12-9.05 (m, 2H), 8.99 (d, 1H), 8.58 (d, 1H), 8.44 (s, 1H), 8.30- 8.21(m, 2H), 8.07 (d, 1H) 368.0 C119

9.13 (t, 1H), 8.64 (d 1H), 8.36-8.30 (m, 1H), 8.16 (d, 1H), 7.98 (d,1H), 3.70 (s, 6H), 2.93- 2.86 (m, 4H), 2.78-2.56 (m, 4H) 485.1 C120

9.48 (s, 1H), 9.27 (s, 2H), 9.09 (t, 1H), 9.00 (d, 1H), 8.59 (d, 1H),8.33 (br. s, 1H), 8.25- 8.17 (m, 1H), 8.10 (d, 1H) 363.1 C121

9.08 (t, 1H), 8.60 (d, 1H), 8.21 (m, 1H), 8.11 (d, 1H), 7.77 (d, 1H),2.52 (m, 2H), 2.40 (s, 3H), 1.14 (t, 3H) 355.1

Physical Characterisation

Compounds of the invention were characterised using one or more of thefollowing methods.

NMR

NMR spectra contained herein were recorded on either a 400 MHz BrukerAVANCE III HD equipped with a Bruker SMART probe or a 500 MHz BrukerAVANCE III equipped with a Bruker Prodigy probe. Chemical shifts areexpressed as ppm downfield from TMS, with an internal reference ofeither TMS or the residual solvent signals. The following multiplicitiesare used to describe the peaks: s=singlet, d=doublet, t=triplet,dd=double doublet, m=multiplet. Additionally br. is used to describe abroad signal and app. is used to describe and apparent multiplicity.

LCMS

LCMS data contained herein consists of the molecular ion [MH+] and theretention time (tr) of the peak recorded on the chromatogram. Thefollowing instruments, methods and conditions were used to obtain LCMSdata:

Method A

Instrumentation; Waters Acquity UPLC-MS using a Sample Organizer withSample Manager FTN, H-Class QSM, Column Manager, 2× Column Manager Aux,Photodiode Array (Wavelength range (nm): 210 to 400, ELSD and SQD 2equipped with a Waters HSS T3 C₁₈ column (column length 30 mm, internaldiameter of column 2.1 mm, particle size 1.8 micron).Ionisation method; Electrospray positive and negative: Capillary (kV)3.00, Cone (V) 30.00, Source Temperature (° C.) 500, Cone Gas Flow(L/Hr.) 10, Desolvation Gas Flow (L/Hr.) 1000. Mass range (Da): positive95 to 800, negative 115 to 800.The analysis was conducted using a two minute run time, according to thefollowing gradient table at 40° C.:

Time (mins) Solvent A (%) Solvent B (%) Flow (ml / mn) 0.00 95.0 5.0 0.71.75 0.0 100 0.7 1.76 0.0 100 0.7 2.0 0.0 5.0 0.7 2.01 95.0 5.0 0.7 2.1195.0 5.0 0.7Solvent A: H₂O with 0.05% TFASolvent B: CH₃CN with 0.05% TFA

Method B (2 Min Method)

Instrumentation; Either (a) Waters Acquity UPLC system with Waters SQD2single-quad MS detector, Photodiode Array Detector (AbsorbanceWavelength: 254 nm, 10 pts/sec, Time Constant: 0.2000 sec), ChargedAerosol Detector (Corona) and Waters CTC 2770 auto-sampler unit(injection volume: 2 microliters, 1 min seal wash); or (b) WatersAcquity UPLC system with Waters QDa single-quad MS detector, PhotodiodeArray Detector (Absorbance Wavelength: 254 nm, 10 pts/sec, TimeConstant: 0.2000 sec), Charged Aerosol Detector (Corona) and Waters CTC2770 auto-sampler unit (injection volume: 2 microliters, 1 min sealwash).

LC-Method;

Phenomenex ‘Kinetex C18 100A’ column (50 mm×4.6 mm, particle size 2.6micron), Flow rate: 2 mL/min at 313K (40 Celsius),Gradient (Solvent A: H₂O with 0.1% Formic Acid; Solvent B: Acetonitrilewith 0.1% Formic Acid):The analysis was conducted using a two minute run time, according to thefollowing gradient table at 40° C.

Time (mins) Solvent A (%) Solvent B (%) Flow (ml / mn) Initial 70.0 30.02.000 1.20 10.0 90.0 2.000 1.70 10.0 90.0 2.000 1.80 70.0 30.0 2.0002.00 70.0 30.0 2.000 2.20 70.0 30.0 2.000

Method C (1 Min Method)

Instrumentation; Either (a) Waters Acquity UPLC system with Waters SQD2single-quad MS detector, Photodiode Array Detector (AbsorbanceWavelength: 254 nm, 10 pts/sec, Time Constant: 0.2000 sec), ChargedAerosol Detector (Corona) and Waters CTC 2770 auto-sampler unit(injection volume: 2 microliters, 1 min seal wash); or (b) WatersAcquity UPLC system with Waters QDa single-quad MS detector, PhotodiodeArray Detector (Absorbance Wavelength: 254 nm, 10 pts/sec, TimeConstant: 0.2000 sec), Charged Aerosol Detector (Corona) and Waters CTC2770 auto-sampler unit (injection volume: 2 microliters, 1 min sealwash).

LC-Method:

Phenomenex ‘Kinetex C18 100A’ column (50 mm×4.6 mm, particle size 2.6micron),Flow rate: 2 mL/min at 313K (40 Celsius),Gradient (Solvent A: H₂O with 0.1% Formic Acid; Solvent B: Acetonitrilewith 0.1% Formic Acid):The analysis was conducted using a one minute run time, according to thefollowing gradient table at 40° C.

Time (mins) Solvent A (%) Solvent B (%) Flow (ml / mn) Initial 60.0 40.02.000 0.80 0.0 100.0 2.000 0.95 0.0 100.0 2.000 1.00 60.0 40.0 2.0001.10 60.0 40.0 2.000 1.25 60.0 40.0 2.000

BIOLOGICAL EXAMPLES B1 Pre-Emergence Herbicidal Activity

Seeds of a variety of test species were sown in standard soil in pots:Triticum aestivium (TRZAW), Avena fatua (AVEFA), Alopecurus myosuroides(ALOMY), Echinochloa crus-galli (ECHCG), Lolium perenne (LOLPE), ZeaMays (ZEAMX), Abutilon theophrasti (ABUTH), Amaranthus retroflexus(AMARE) and Setaria faberi (SETFA). After cultivation for one day(pre-emergence) under controlled conditions in a glasshouse (at 24/16°C., day/night; 14 hours light; 65% humidity), the plants were sprayedwith an aqueous spray solution derived from the formulation of thetechnical active ingredient in acetone/water (50:50) solution containing0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5).The test plants were then grown in a glasshouse under controlledconditions (at 24/16° C., day/night; 14 hours light; 65% humidity) andwatered twice daily. After 13 days, the test was evaluated (5=totaldamage to plant; 0=no damage to plant). Results are shown in Tables B1aand B1b.

Tables B1a and B1b Control of Weed Species by Compound of Formula (I)after Pre-Emergence Application

TABLE B1a Test 1a Com- pound Rate ID (g/ha) LOLPE SETFA ALOMY ECHCGAVEFA TRAZW C1 1000 1 5 0 5 2 1 C2 1000 1 5 0 3 0 0 C3 1000 1 5 0 4 0 0C4 1000 5 1 0 4 1 0 C5 1000 1 5 1 4 3 0 C6 1000 2 4 1 4 4 1 C7 1000 1 40 4 3 0 C8 1000 2 5 0 4 3 0 C11 1000 1 4 0 1 0 0 C12 1000 1 4 0 2 0 0C13 1000 3 5 1 4 2 0 C14 1000 2 4 2 5 1 0 C15 1000 1 5 0 5 0 0 C16 10002 5 0 4 1 0 C17 1000 1 5 0 4 3 0 C19 1000 0 5 0 3 2 0 C20 1000 0 5 0 4 20 C21 1000 1 5 0 4 2 0 C22 1000 1 5 0 4 2 0 C23 1000 1 5 1 5 3 1 C241000 1 5 1 4 4 0 C26 1000 1 5 0 5 2 0 C27 1000 1 5 0 5 3 0 C28 1000 1 40 4 3 0 C29 1000 1 5 0 5 4 0 C30 1000 1 5 2 5 3 0 C31 1000 0 5 1 4 2 0C33 1000 1 2 0 1 1 0 C34 1000 0 5 0 2 0 0 C35 1000 1 4 0 4 1 0 C36 10001 4 0 4 1 0 C37 1000 1 5 0 4 1 0 C38 1000 0 5 0 4 0 0 C39 1000 1 5 0 4 20 C40 1000 0 3 0 1 0 0 C42 1000 1 4 0 4 2 0 C44 1000 1 4 0 5 2 0 C451000 1 4 0 5 2 0 C46 1000 1 4 0 2 1 0 C47 1000 1 4 1 5 2 0 C49 1000 1 51 5 2 0 C50 1000 1 4 0 3 1 0 C51 1000 0 4 0 3 0 0 C52 1000 1 5 1 4 1 0C53 1000 1 4 1 5 3 0 C54 1000 1 3 0 2 1 0 C55 1000 1 4 0 1 1 0 C56 10000 4 0 3 1 0 C57 1000 0 4 0 3 1 0 C58 1000 0 5 0 3 0 0 C59 1000 1 5 0 4 30 C60 1000 0 5 0 3 2 0 C61 1000 0 5 0 3 1 0 C62 1000 1 4 0 3 2 0 C631000 1 4 0 2 0 0 C65 1000 2 3 0 4 3 0 C67 1000 0 2 0 1 0 0 C69 1000 0 50 3 1 0 C70 1000 1 2 0 2 1 0 C71 1000 1 5 0 4 1 1 C72 1000 0 4 0 1 0 0C73 1000 0 5 0 4 2 0 C74 1000 1 3 1 1 0 0 C76 1000 0 5 0 1 0 0 C77 10000 1 0 0 0 0 C78 1000 0 2 0 1 0 0 C79 1000 2 5 0 3 1 0 C80 1000 0 3 0 2 10 C81 1000 2 5 0 3 1 0 C82 1000 0 1 0 1 0 0 C83 1000 1 4 0 2 1 0 C841000 1 5 0 2 1 0 C85 1000 0 2 0 2 0 0 C86 1000 0 1 0 0 0 0 C87 1000 0 50 2 0 0 C88 1000 0 2 0 1 0 0 C89 1000 0 4 0 3 1 0 C90 1000 0 2 0 2 0 0C94 1000 1 5 0 2 1 0 C95 1000 1 4 0 3 1 0 C96 1000 0 5 1 3 1 0 C97 10000 3 0 1 0 0 C98 1000 1 3 0 1 0 0 C99 1000 1 5 0 2 1 0 C100 1000 1 5 0 31 0 C101 1000 0 1 0 1 1 0 C102 1000 0 4 0 2 1 0 C103 1000 0 1 0 0 0 0C104 250 0 3 0 0 0 0 C106 1000 1 4 0 3 2 0 C107 1000 0 5 0 3 1 0 C1081000 1 5 0 2 1 0 C109 1000 1 4 0 4 2 0 C110 1000 1 4 0 4 3 0 C111 1000 15 1 4 2 0 C112 1000 1 4 1 3 2 0 C113 1000 1 5 0 5 2 0 C114 1000 0 5 0 41 0 C115 1000 1 5 0 5 0 0 C116 1000 0 5 0 3 1 NT C117 250 0 2 0 1 0 0C119 1000 1 5 0 5 2 0 C120 1000 1 5 0 4 3 0 C121 250 1 5 0 3 2 0

TABLE B1b Test 1b - Com- pound Rate ID (g/ha) LOLPE AMARE SETFA ECHCGZEAMX ABUTH C9 1000 2 2 4 3 5 1 C10 1000 2 0 4 4 5 1

B2 Post-Emergence Herbicidal Activity

Seeds of a variety of test species were sown in standard soil in pots:Triticum aestivium (TRZAW), Avena fatua (AVEFA), Alopecurus myosuroides(ALOMY), Echinochloa crus-galli (ECHCG), Lolium perenne (LOLPE), ZeaMays (ZEAMX), Abutilon theophrasti (ABUTH), Amaranthus retroflexus(AMARE) and Setaria faberi (SETFA). After 8 days cultivation(post-emergence) under controlled conditions in a glasshouse (at 24/16°C., day/night; 14 hours light; 65% humidity), the plants were sprayedwith an aqueous spray solution derived from the formulation of thetechnical active ingredient in acetone/water (50:50) solution containing0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5).The test plants were then grown in a glasshouse under controlledconditions (at 24/16° C., day/night; 14 hours light; 65% humidity) andwatered twice daily. After 13 days, the test was evaluated (5=totaldamage to plant; 0=no damage to plant). Results are shown in Tables B2aand B2b.

Tables B2a and B2b Control of Weed Species by Compound of Formula (I)after Post-Emergence Application

TABLE B2a Test 2a Com- pound Rate ID (g/ha) LOLPE SETFA ALOMY ECHCGAVEFA TRAZW C1 1000 4 5 1 5 3 1 C2 1000 2 5 1 5 3 1 C3 1000 3 5 1 5 3 1C4 1000 5 3 1 4 4 1 C5 1000 4 5 1 4 4 0 C6 1000 4 5 1 4 4 1 C7 1000 3 51 4 4 1 C8 1000 2 5 3 4 4 2 C11 1000 1 5 1 3 2 0 C12 1000 2 5 1 5 3 0C13 1000 4 5 1 5 4 0 C14 1000 4 5 1 5 4 1 C15 1000 3 5 1 5 3 1 C16 10003 5 1 5 4 1 C17 1000 2 NT 0 5 3 0 C19 1000 1 NT 0 4 3 0 C20 1000 2 NT 04 3 0 C21 1000 2 NT 0 5 3 0 C22 1000 2 NT 0 4 3 0 C23 1000 3 5 0 5 3 0C24 1000 4 5 1 5 4 1 C26 1000 4 5 0 5 4 1 C27 1000 3 5 1 5 4 1 C28 10003 5 0 5 4 0 C29 1000 3 5 0 5 4 0 C30 1000 3 5 0 5 4 0 C31 1000 3 5 0 5 30 C33 1000 1 3 0 2 2 0 C34 1000 2 5 1 4 3 1 C35 1000 2 5 0 5 3 0 C361000 1 5 0 5 2 1 C37 1000 2 5 0 5 3 0 C38 1000 2 5 0 4 3 0 C39 1000 2 50 5 3 1 C40 1000 2 5 0 3 3 0 C42 1000 2 5 0 5 4 1 C44 1000 3 5 1 5 3 0C45 1000 2 5 0 5 2 1 C46 1000 1 4 0 3 2 0 C47 1000 3 5 1 5 4 0 C49 10003 5 1 5 4 0 C50 1000 1 4 1 2 3 0 C51 1000 1 4 0 2 2 0 C52 1000 2 5 0 4 40 C53 1000 4 5 0 5 4 1 C54 1000 3 4 1 5 3 0 C55 1000 2 4 1 4 3 0 C561000 2 4 0 4 3 1 C57 1000 2 4 0 4 2 0 C58 1000 1 5 0 4 2 0 C59 1000 3 41 5 3 0 C60 1000 3 4 0 4 3 0 C61 1000 2 4 1 4 2 0 C62 1000 2 5 1 5 4 1C63 1000 2 4 1 4 2 0 C65 1000 3 5 0 5 4 0 C67 1000 2 4 0 4 2 0 C69 1000NT 4 0 3 NT 0 C70 1000 1 3 0 2 2 0 C71 1000 NT 5 0 4 NT 0 C72 1000 NT 30 2 NT 0 C73 1000 NT 5 0 4 NT 0 C74 1000 NT 3 0 2 NT 0 C76 1000 NT 4 0 3NT 1 C77 1000 NT 2 0 1 NT 0 C78 1000 NT 3 0 1 NT 0 C79 1000 NT 3 0 3 NT0 C80 1000 1 5 1 3 2 1 C81 1000 NT 5 0 4 NT 0 C82 1000 NT 2 0 1 NT 0 C831000 NT 3 0 2 NT 0 C84 1000 NT 4 1 3 NT 0 C85 1000 1 4 0 4 2 1 C86 1000NT 1 0 1 NT 0 C87 1000 NT 4 0 3 NT 0 C88 1000 1 2 1 1 1 1 C89 1000 NT 40 4 NT 0 C90 1000 1 4 0 4 2 1 C94 1000 2 5 0 4 2 0 C95 1000 2 5 1 5 2 1C96 1000 NT 4 0 3 NT 0 C97 1000 NT 3 0 2 NT 0 C98 1000 NT 0 0 1 NT 0 C991000 2 5 0 4 2 0 C100 1000 NT 5 0 4 NT 0 C101 1000 NT 2 0 2 NT 0 C1021000 NT 2 0 2 NT 0 C103 1000 1 2 0 1 2 0 C104 250 NT 2 0 1 NT 0 C1061000 NT 5 0 4 NT 0 C107 1000 NT 5 0 4 NT 0 C108 1000 NT 4 0 3 NT 0 C1091000 2 5 0 5 3 1 C110 1000 2 5 0 5 3 1 C111 1000 2 5 1 5 4 0 C112 1000 31 0 4 3 1 C113 1000 3 5 1 5 4 3 C114 1000 1 5 1 4 2 1 C115 1000 1 5 0 42 0 C116 1000 1 5 0 4 2 0 C117 250 1 4 1 1 3 0 C119 1000 3 5 1 5 4 3C120 1000 3 5 1 5 3 2 C121 250 3 5 1 4 4 1

TABLE B2b Test 2b - Com- pound Rate ID (g/ha) LOLPE AMARE SETFA ECHCGZEAMX ABUTH C9 1000 3 2 5 4 5 2 C10 1000 3 1 4 4 5 1

1. A method of controlling weeds at a locus, said method comprisingapplying to the locus a weed-controlling amount of a compound of formula(I)

or a salt or N-oxide thereof, wherein, X¹ is N or CR¹; R¹ is selectedfrom the group consisting of hydrogen, halogen, cyano, C₁-C₆alkyl,C₃-C₆cycloalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆alkoxy,—C(O)OC₁-C₆alkyl, —S(O)_(p)C₁-C₆alkyl, NR⁶R⁷, C₁-C₆haloalkoxy andC₁-C₆haloalkyl; R² is selected from the group consisting of halogen,cyano, nitro, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,C₃-C₆cycloalkyl, —C(O)OC₁-C₆alkyl, —S(O)_(p)(C₁-C₆alkyl), C₁-C₆alkoxyand C₁-C₆haloalkoxy; R³ is —C(O)R⁹; R⁴ is selected from the groupconsisting of hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆alkenyl,C₃-C₆alkynyl, C_(r)alkoxyC_(s)alkyl, -C_(r)alkoxyC_(s)haloalkyl,C_(r)alkoxyC_(s)thioalkyl, —C(O)R⁹ and —(CR^(a)R^(b))_(q)R⁵; each R^(a)is independently hydrogen or C₁-C₂ alkyl; each R^(b) is independentlyhydrogen or C₁-C₂ alkyl; R^(c) is hydrogen or C₁-C₄alkyl; R⁵ is—C(O)OC₁-C₆alkyl, —C₃-C₆cycloalkyl, cyano, —NR⁶R⁷, —C(O)NR^(a)R^(b),—S(O)_(p)(R¹¹)_(n), -aryl or -heteroaryl wherein said aryl andheteroaryl are optionally substituted by 1 to 3 independent R⁸; R⁶ andR⁷ are independently selected from the group consisting of hydrogen andC₁-C₆alkyl; each R⁸ is independently selected from the group consistingof halogen, C₁-C₆ alkyl and C₁-C₆alkoxy-, C₁-C₆ haloalkyl, C₁-C₆haloalkoxy-, cyano and S(O)_(p)(C₁-C₆alkyl); each R⁹ is independentlyselected from the group consisting of hydrogen, C₁-C₆alkyl,C_(r)alkoxyC_(s)alkyl, C₁-C₆haloalkyl, C_(r)alkoxyC_(s)haloalkyl,C₂-C₆alkenyl, C₂-C₆alkynyl, and —(CR^(a)R^(b))_(q)R¹⁰; or R⁴ and R⁹together with the atoms to which they are joined form a 5-7 memberedring system containing from 1 to 3 heteroatoms, wherein at least oneheteroatom is N, and any additional heteroatom is independently selectedfrom S, O and N; R¹⁰ is —C(O)OR^(c), —OC(O)R^(c), —C₃-C₆cycloalkyl, oran -aryl, -aryloxy, -heteroaryl, -heteroaryloxy or -heterocyclyl ring,wherein said ring is optionally substituted by 1 to 3 independent R⁸;each n is independently 0 or 1; p is 0, 1, or 2; each q is independently0, 1,2, 3, 4, 5 or 6; r is 1,2, 3, 4, or 5; s is 1,2, 3, 4, or 5, andthe sum of r+s is less than or equal to 6; and, R¹¹ is C₁-C₆alkyl. 2.The method of claim 1, wherein X¹ is N.
 3. The method of claim 1,wherein X¹ is CR¹ and R¹ is halogen or cyano.
 4. The method of claim 1,wherein R² is halogen, cyano, C₁-C₆alkyl or C₁-C₆haloalkyl.
 5. Themethod of claim 1, wherein R³ is —C(O)C₁-C₆alkyl, —C(O)C₁-C₃haloalkyl,—C(O)C₁-C₃alkoxyC₁-C₃alkyl or —C(O)(CR^(a)R^(b))_(q)R¹⁰.
 6. The methodof claim 5, wherein R¹⁰ is —C(O)OR^(c), —OC(O)R^(c), cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, or a ring system selected fromphenyl, phenoxy, pyridinyl, pyrimidinyl, thiazolyl, and thiophenyl,wherein said ring system is optionally substituted by 1-3 independentR⁸.
 7. The method of claim 1, wherein R⁴ is selected from the groupconsisting of hydrogen, C₁-C₄alkyl, C₃-C₆alkenyl, C_(r)alkoxyC_(s)alkyl,C_(r)alkylthioC_(s)alkyl, C₃-C₆alkynyl, C₁-C₃haloalkyl,C_(r)alkoxyC_(s)haloalkyl, —C(O)R⁹, and —(CR^(a)R^(b))_(q)R⁵.
 8. Themethod of claim 7, wherein R⁴ is —C(O)C₁-C₃alkyl, —C(O)C₂-C₄alkenyl, or—C(O)(CR^(a)R^(b))_(q)R¹⁰.
 9. The method of claim 7, wherein R⁴ is—(CR^(a)R^(b))_(q)R⁵, wherein q is 1,2, or 3; R^(a) and R^(b) areindependently hydrogen, methyl or ethyl; and, R⁵ is —C(O)NR^(a)R^(b),—NR⁶R⁷, cyano, —C₃-C₆cycloalkyl, -aryl or -heteroaryl, wherein said aryland heteroaryl are optionally substituted by 1 to 3 independent R⁸. 10.The method of claim 1, wherein said weeds are of a genus selected fromthe group consisting of Brachiaria, Cenchrus, Digitaria, Echinochloa,Eleusine, Eriochloa, Panicum, Setaria, Sorghum, and volunteer Zea mays.11. The method of claim 1, wherein the weed-controlling amount of thecompound of formula (I) is applied to said locus at a rate of between 50g/Ha and 1000 g/Ha.
 12. The method of claim 1 wherein the weedcontrolling amount of a compound of formula (I) is applied to said locusin combination with a further herbicide.
 13. A herbicidal compositioncomprising from 0.1 to 99% by weight of an active ingredient and from 1to 99.9% by weight of a formulation adjuvant, wherein said activeingredient consists of either (i) a compound of formula (I),

or a salt or N-oxide thereof, wherein, X¹ is N or CR¹; R¹ is selectedfrom the group consisting of hydrogen, halogen, cyano, C₁-C₆alkyl,C₃-C₆cycloalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆alkoxy,—C(O)OC₁-C₆alkyl, —S(O)_(p)C₁-C₆alkyl, NR⁶R⁷, C₁-C₆haloalkoxy andC₁-C₆haloalkyl; R² is selected from the group consisting of halogen,cyano, nitro, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,C₃-C₆cycloalkyl, —C(O)OC₁-C₆alkyl, —S(O)_(p)(C₁-C₆alkyl), C₁-C₆alkoxyand C₁-C₆haloalkoxy; R³ is —C(O)R⁹; R⁴ is selected from the groupconsisting of hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆alkenyl,C₃-C₆alkynyl, C_(r)alkoxyC_(s)alkyl, —C_(r)alkoxyC_(s)haloalkyl,C_(r)alkoxyC_(s)thioalkyl, —C(O)R⁹ and —(CR^(a)R^(b))_(q)R⁵; each R^(a)is independently hydrogen or C₁-C₂ alkyl; each R^(b) is independentlyhydrogen or C₁-C₂ alkyl; R^(c) is hydrogen or C₁-C₄alkyl; R⁵ is—C(O)OC₁-C₆alkyl, —C₃-C₆cycloalkyl, cyano, —NR⁶R⁷, —C(O)NR^(a)R^(b),—S(O)_(p)(R¹¹)_(n), -aryl or -heteroaryl wherein said aryl andheteroaryl are optionally substituted by 1 to 3 independent R⁸; R⁶ andR⁷ are independently selected from the group consisting of hydrogen andC₁-C₆alkyl; each R⁸ is independently selected from the group consistingof halogen, C₁-C₆ alkyl and C₁-C₆alkoxy-, C₁-C₆ haloalkyl, C₁-C₆haloalkoxy-, cyano and S(O)_(p)(C₁-C₆alkyl); each R⁹ is independentlyselected from the group consisting of hydrogen, C₁-C₆alkyl,C_(r)alkoxyC_(s)alkyl, C₁-C₆haloalkyl, C_(r)alkoxyC_(s)haloalkyl,C₂-C₆alkenyl, C₂-C_(s)alkynyl, and —(CR^(a)R^(b))_(q)R¹⁰; or R⁴ and R⁹together with the atoms to which they are joined form a 5-7 memberedring system containing from 1 to 3 heteroatoms, wherein at least oneheteroatom is N, and any additional heteroatom is independently selectedfrom S, O and N; R¹⁰ is —C(O)OR^(c), —OC(O)R^(c), —C₃-C₆cycloalkyl, oran -aryl, -aryloxy, -heteroaryl, -heteroaryloxy or -heterocyclyl ring,wherein said ring is optionally substituted by 1 to 3 independent R⁸;each n is independently 0 or 1; p is 0, 1, or 2; each q is independently0,1,2, 3, 4, 5 or 6; r is 1,2, 3, 4, or 5; s is 1,2, 3, 4, or 5, and thesum of r+s is less than or equal to 6; and, R¹¹ is C₁-C₆alkyl, or (ii) acompound of formula (I) as defined in (i) and a further herbicide, or(iii) a compound of formula (I) as defined in (i) and a safener, andwherein the formulation adjuvant includes from 0 to 25% by weight of asurface-active substance.
 14. The herbicidal composition of claim 13,wherein the surface active agent is a cationic, anionic, amphoteric ornon-ionic type surface active agent.
 15. The herbicidal composition ofclaim 13, wherein the further herbicide is selected from the groupconsisting of
 16. The herbicidal composition of claim 13, wherein thesafener is selected from the group consisting of
 17. The method of claim1, wherein the compound of formula (I) is in the form of the compositionof claim 13.